Search | Preprints.org

Preprint ARTICLE | doi:10.20944/preprints201607.0025.v1

Broad Band Observations Of Gravitationally Lensed Blazar QSO B0218+357 During A Gamma-Ray Outburst

Julian Sitarek, Josefa Becerra González, Sara Buson, Dijana Dominis Prester, Marina Manganaro, Daniel Mazin, Kari Nilsson, Mireia Nievas, Antonio Stamerra, Fabrizio Tavecchio, Ievgen Vovk

Subject: Physical Sciences, Astronomy And Astrophysics Keywords: Gamma rays: galaxies; Gravitational lensing: strong; Galaxies: jets; Radiation mechanisms: non-thermal; Galaxies: individual: QSO B0218+357

Online: 13 July 2016 (05:36:15 CEST)

Show abstract| Download PDF| Share

Preprint HYPOTHESIS | doi:10.20944/preprints202104.0606.v2

Role of a-Synuclein in Cell Biology: A Hypothesis and its Implications in Neurodegenerative Diseases

Renu Minda

Subject: Biology And Life Sciences, Biophysics Keywords: Parkinson’s disease; alpha-synuclein; Lewy bodies; phase transition; thermodynamics; and mitochondria

Online: 10 January 2022 (12:23:19 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201703.0116.v1

Potent Natural Inhibitors of Alpha-Glucosidase and Alpha-Amylase against Hyperglycemia in Vitro and in Vivo

Jirawat Riyaphan, Chien-Hung Jhong, May-Jwan Tsai, Der-Nan Lee, Max K. Leong, Ching-Feng Weng

Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: In vivo; Alpha-glucosidase; Alpha-amylase; hyperglycemia

Online: 16 March 2017 (09:35:36 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202007.0239.v1

Fundamental Constants in Time from the Big-Bang

Heikki Sipilä, Ari Lehto

Subject: Physical Sciences, Astronomy And Astrophysics Keywords: Fine structure constant; period doubling; alpha; natural constants

Online: 11 July 2020 (10:23:28 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201609.0073.v1

Strategies in the Design of Antidiabetic Drugs from Terminalia Chebula Retz. Using in silico and in vitro Approach

Twinkle Bansode, B.K. Salalkar

Subject: Medicine And Pharmacology, Endocrinology And Metabolism Keywords: diabetes mellitus, molecular docking, thin layer chromatography, alpha amylase, ellagic acid

Online: 20 September 2016 (16:13:12 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201807.0224.v2

Pseudopterosin Inhibits Proliferation and 3D Invasion in Triple Negative Breast Cancer by Agonizing Glucocorticoid Receptor Alpha

Julia Sperlich, Nicole Teusch

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: pseudopterosin; triple negative breast cancer; glucocorticoid receptor alpha; dexamethasone; cell proliferation; 3D invasion; tumor spheroid; co-culture; interleukin 6; interleukin 8

Online: 2 August 2018 (06:08:31 CEST)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints201702.0020.v1

Potential Modes of Intercellular Alpha-Synuclein Transmission

Dario Valdinocci, Rowan A. W. Radford, Sue Maye Siow, Roger S. Chung, Dean L. Pountney

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: alpha-synuclein; Parkinsons disease; dementia with Lewy bodies; multiple system atrophy; tunelling nanotube; glymphatic system; cell-to-cell spread

Online: 7 February 2017 (03:24:21 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201907.0326.v2

Demonstration to Unify 4 Interactions in Particle Physics with the Zero‐Point Energy and Quantized Spacetime

Shinichi Ishiguri

Subject: Physical Sciences, Particle And Field Physics Keywords: zero‐point energy; quantized spacetime; static electromagnetic field; gravity field; weak interaction; strong interaction; masses of W and Z; β collapse; quantized Einstein gravity equation

Online: 9 November 2023 (13:40:49 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201710.0180.v1

Low Levels of IgG Recognizing the Alpha-1-Antitrypsin (A1AT) ^50-63 Peptide and Its Association with Taiwanese Women with Primary Sjögren's Syndrome

Yu-Sheng Chang, Chih-Hong Pan, Che-Chang Chang, Kai-Leun Tsai, Han-Wen Chou, Jin-Hua Chen, Sheng-Hong Lin, Yi-Ying Lu, Chih-Chun Tai, Yi-Fang Lin, Ching-Yu Lin

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: primary Sjögren's syndrome; alpha-1-antitrypsin; inhibitor; 4-hydroxy-2-nonenal; autoantibody isotypes; serum

Online: 30 October 2017 (04:30:59 CET)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints201804.0365.v1

Enantioselective Organocatalyzed a-Amination of 1,3-Dicarbonyl Compounds in Deep Eutectic Mixtures

Diego Ros Ñíguez, Pegah Khazaeli, Diego A. Alonso, Gabriela Guillena

Subject: Chemistry And Materials Science, Organic Chemistry Keywords: asymmetric organocatalysis; benzimidazole; alpha-Amination; deep eutectic solvents; green chemistry, natural products

Online: 27 April 2018 (16:23:02 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201906.0052.v1

SerThr-PhosphoProteome of Brain from Aged PINK1-KO+A53T-SNCA Mice Reveals pT1928-MAP1B and pS3781-ANK2 Deficits, as Hub between Autophagy and Synapse Changes

Georg Auburger, Suzana Gispert, Sylvia Torres-Odio, Marina Jendrach, Nadine Brehm, Júlia Canet-Pons, Jana Key, Nesli-Ece Sen

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Parkinson's disease; brain phosphorylome; PINK1, alpha-synuclein; microtubular cytoskeleton; autophagy; synaptic signaling

Online: 7 June 2019 (03:21:19 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Hereditary Parkinson’s disease (PD) can be triggered by an autosomal dominant overdose of alpha-Synuclein (SNCA) as stressor or the autosomal recessive deficiency of PINK1 Serine/Threonine-phosphorylation activity as stress-response. We demonstrated the combination of PINK1-knockout with overexpression of SNCAA53T in double mutant (DM) mice to exacerbate locomotor deficits and to reduce lifespan. To survey posttranslational modifications of proteins underlying the pathology, brain hemispheres of old DM mice underwent quantitative label-free global proteomic mass spectrometry, focused on Ser/Thr-phosphorylations. As exceptionally strong effect, we detected >300-fold reductions of phosphoThr1928 in MAP1B, a microtubule-associated protein, and a similar reduction of phosphoSer3781 in ANK2, an interactor of microtubules. MAP1B depletion is known to trigger perturbations of microtubular mitochondria trafficking, neurite extension and synaptic function, so it was noteworthy that relevantly decreased phosphorylation was detected also for other microtubule and microfilament factors, namely MAP2S1801, MARK1S394, MAP1AT1794, KIF1AS1537, 4.1NS541, 4.1GS86 and ADD2S528. While the MAP1B heavy chain supports regeneration and growth cones, its light-chain assists DAPK1-mediated autophagy. Interestingly, relevant phosphorylation decreases of DAPK2S299, VPS13DS2429 and VPS13CS2480 in the DM brain affected regulators of autophagy, which are implicated in PD. Overall, significant downregulations were enriched for PFAM C2 domains, other kinases, and synaptic transmission factors upon automated bioinformatics, while upregulations were not enriched for selective motifs or pathways. Validation experiments confirmed the change of LC3 processing as reflection of excessive autophagy in DM brain, and dependence of ANK2/MAP1B expression on PINK1 levels. Our new data provide independent confirmation in a mouse model with combined PARK1/PARK4/PARK6 pathology that MAP1B/ANK2 phosphorylation events are implicated in Parkinsonian neurodegeneration. These findings expand on previous observations in D. melanogaster that the MAP1B ortholog futsch in the presynapse is a primary target of the PARK8 protein LRRK2, and on a report that MAP1B is a component of the pathological Lewy body aggregates in PD patient brains. Similarly, ANK2 gene locus variants are associated with the risk of PD, ANK2 interacts with PINK1/Parkin-target proteins such as MIRO1 or ATP1A2, and ANK2-derived peptides are potent inhibitors of autophagy.

Preprint ARTICLE | doi:10.20944/preprints202206.0256.v1

Unified Theory of Gravity, Electromagnetic Force, Strong and Weak Forces and Their Applications

Sheng Qin

Subject: Physical Sciences, Particle And Field Physics Keywords: unified theory of force; Gravitation; Electromagnetic force; Weak force; Strong force; Inverse square law; Galaxy rotation curve; The origin of magnetic field; Charged particle radiation; Maxwell displacement current; Black hole structure; Radiation effect of moving magnet

Online: 20 June 2022 (03:03:59 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202109.0302.v2

Gravitational Field and Mass

Yin Zhu

Subject: Physical Sciences, Particle And Field Physics Keywords: Super strong gravitational field; Mass-Gravitational field conversion; Graviton-photon conversion; Graviton-photon to electron-proton conversion; Vacuum fluctuation; Vacuum polarization

Online: 1 December 2021 (12:49:09 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201709.0100.v1

Cut-off Values of Hematologic Parameters to Predict the Number of Alpha Genes Deleted in Subjects with Deletional Alpha Thalassemia

Diego Velasco-Rodríguez, Carlos Blas, Juan-Manuel Alonso-Domínguez, Gala Vega, Carlos Soto, Aránzazu García-Raso, Pilar Llamas-Sillero

Subject: Medicine And Pharmacology, Hematology Keywords: alpha; thalassemia; deletional; cut-off; number of genes; microcytic anemia; differential diagnosis

Online: 21 September 2017 (04:47:16 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201710.0075.v1

Understanding Nuclear Binding Energy with Strong and Electroweak Coupling Constants

U.V. Satya Seshavatharam, S. Lakshminarayana

Subject: Physical Sciences, Nuclear And High Energy Physics Keywords: nuclear charge radius; strong coupling constant; Fermi’s weak coupling constant; nuclear binding energy coefficient

Online: 12 October 2017 (04:39:19 CEST)

Show abstract| Download PDF| Share

At nuclear scale, we present three heuristic relations pertaining to strong and electroweak coupling constants. With these relations, close to beta stability line, it is possible to study nuclear binding energy with a single energy coefficient of magnitude

(\frac{1}{α_{s}}) [\frac{e^{2}}{4 π ε_{0} R_{0}}] \approx 10.0 MeV .

With reference to up and down quark masses, it is also possible to interpret that, nuclear binding energy is proportional to the mean mass of

[(2 m_{u} + m_{d}) and (m_{u} + 2 m_{d})] \approx 10.0 MeV .

Preprint REVIEW | doi:10.20944/preprints202103.0699.v1

Bismuth-213 for Targeted Radionuclide Therapy: From Atom to Bedside

Stephen Ahenkorah, Irwin Cassells, Christophe M Deroose, Thomas Cardinaels, Andrew R Burgoyne, Guy Bormans, Maarten Ooms, Frederik Cleeren

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Bismuth-213; Targeted Radionuclide Therapy; Targeted alpha Therapy; radiopharmaceutical; bifunctional chelator; vector molecule

Online: 29 March 2021 (14:43:57 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201809.0058.v1

Integrative Proteomic and Metabolomic Analysis Reveals the Cotton Plant Defense Mechanisms Induced by Insect (Adelphocoris suturalis Jakovlev) Feeding

Hui Lu, Shuai Zhang, Junyu Luo, Chunyi Wang, Limin Lv, Lijuan Zhang, Xiangzhen Zhu, Li Wang, Xueke Gao, Hongxia Hua, Jinjie Cui

Subject: Biology And Life Sciences, Plant Sciences Keywords: Gossypium hirsutum L.; Adelphocoris suturalis (Jakovlev); alpha-linolenic acid pathway; tryptophan metabolism; plant defence

Online: 4 September 2018 (06:29:16 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint COMMUNICATION | doi:10.20944/preprints202109.0133.v1

Fluid and Tissue Biomarkers of Lewy Body Dementia: Report of an LBDA Symposium

Gregory D. Scott, Moriah R. Arnold, Thomas G. Beach, Christopher H. Gibbons, Anumantha G. Kanthasamy, Russell M. Lebovitz, Afina W. Lemstra, Leslie M. Shaw, Charlotte E. Teunissen, Henrik Zetterberg, Angela S. Taylor, Todd C. Graham, Bradley F. Boeve, Stephen N. Gomperts, Neill R. Graff-Radford, Charbel E.-H. Moussa, Kathleen L. Poston, Liana S. Rosenthal, Marwan N. Sabbagh, Ryan R. Walsh, Miriam T. Weber, Melissa J. Armstrong, Jee A. Bang, Andrea C. Bozoki, Kimiko Domoto-Reilly, John E. Duda, Jori E. Fleisher, Douglas R. Galasko, James E. Galvin, Jennifer G. Goldman, Samantha K. Holden, Lawrence S. Honig, Daniel E. Huddleston, James B. Leverenz, Irene Litvan, Carol A. Manning, Karen S. Marder, Alexander Y. Pantelyat, Victoria S. Pelak, Douglas W. Scharre, Sharon J. Sha, Holly A. Shill, Mari Zoltan, Joseph F. Quinn, David J. Irwin

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: cerebrospinal fluid; alpha-synuclein; skin biopsy; seeded aggregation assays; tau, amyloid; Lewy body dementia

Online: 7 September 2021 (16:26:51 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201902.0167.v1

Spatially Resolved Soil Solution Chemistry in a Central European Atmospherically Polluted High-Elevation Catchment

Daniel Petrash, Frantisek Buzek, Martin Novak, Bohuslava Cejkova, Pavel Kram, Tomas Chuman, Jan Curik, Frantisek Veselovsky, Marketa Stepanova, Oldrich Myska, Pavla Holeckova, Leona Bohdalkova

Subject: Environmental And Earth Sciences, Environmental Science Keywords: Anions of strong acids; Base cations; Entic podzol; Lysimeter • Small catchment; Soil solutions

Online: 18 February 2019 (17:01:18 CET)

Show abstract| Download PDF| Supplementary Files| Share

Here we evaluate the chemistry of mineral soil solutions collected by suction lysimeters in a small mountain catchment that was affected by acidification-related spruce die-back. The aim was to obtain new insights into spatial patterns of nutrient partitioning during acidification recovery. This was achieved by comparing nutrient concentrations in soil solutions, collected along a V-shaped valley, with those in runoff. Five nests of suction lysimeters were installed in the 33-ha UDL catchment at different topographic positions (hilltops, slopes and valley). Following a 1-year equilibration, monthly samples of soil solutions were collected over a 2-year period. In the vicinity of each lysimeter nest, soil pits were excavated for a study of soil chemistry. Soil solutions were analyzed for SO42-, NO3-, DOC, NH4+, Na+, K+, Ca2+, Mg2+, and total dissolved Al concentrations, DOC and pH. For a P release estimation, ammonium oxalate extraction of soil samples was performed. Comparison of soil water data from this study with other European studies indicated that major environmentally relevant chemical species at UDL had concentrations similar to median concentrations across numerous previously acidified sites. CEC (≤ 58 meq kg-1) and BS (≤ 13 %), however, were significantly lower at UDL than at other European sites, documenting incomplete recovery from acidification. Spatial trends and seasonality in soil water chemistry support belowground inputs from mineral-stabilized legacy pollutants and soil nutrients. Seasonal variability of soil water sulfate and nitrate was significant. High nitrate in soil solutions during summer originated during the preceding dormant season, and high sulfate concentrations observed during the winter originating from recycled organic S during the summer. Higher concentrations of SO42-, NO3-, and base cations in runoff than in soil solutions may be explained by lateral surficial runoff leaching pollutants and nutrients from very shallow soil horizons. Nearly 30 years after peak acidification, solutions in mineral subsoil at UDL exhibited similar concentrations of SO42-, Ca2+ and Mg2+ as median values at the Pan-European International Co-operative Program (ICP) Forest sites, yet NO3- concentrations were an order of magnitude higher than the ICP sites. Calcium applied on soil surface by liming 32 to 11 years ago affected runoff more than soil solutions, suggesting contribution of both shallow soil water and groundwater to runoff.

Preprint ARTICLE | doi:10.20944/preprints201712.0079.v1

Fuzzifying Strongly Compact Spaces and Fuzzifying Locally Strongly Compact Spaces

O. R. Sayed, Adem Kiliҫman

Subject: Computer Science And Mathematics, Logic Keywords: Łukasiewicz logic; semantics; fuzzifying topology; fuzzifying compactness; strong compactness; fuzzifying locally compactness; locally strong compactness

Online: 13 December 2017 (06:43:52 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201909.0130.v1

Synthesis of novel Triazinoindole-Based-Thiourea Hybrid: α-Glucosidase Inhibitors and Their Molecular Docking Study

Muhammad Taha, Foziah J. Alshamrani, Fazal Rahim, Shawkat Hayat, Hayat Ullah, Khalid Zaman, Syahrul Imran

Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: Synthesis; triazinoindole; thiosemicarbazide; alpha-glucosidase; molecular docking study; SAR

Online: 13 September 2019 (10:54:30 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202001.0038.v1

Responses of Individual Plant Species, Functional Groups, α- and β-Diversity to Short-Term Grazing Exclusion under Severe Drought Episode in Long-Term Grazed Alfa-Steppes

Yacine Kouba, Saifi Merdes, Badreddine Saadali, Haroun Chenchouni

Subject: Biology And Life Sciences, Ecology, Evolution, Behavior And Systematics Keywords: Mediterranean steppes; drylands; alpha diversity; beta diversity; rangeland grazing; indicator species

Online: 5 January 2020 (15:22:33 CET)

Show abstract| Download PDF| Share

Grazing exclusion has been proved to be one of the main measures for rehabilitating degraded arid steppes. However, the effect of this management practice on plant species diversity and composition is ambiguous, specially under prolonged droughts. Concurrently considering the responses of individual plant species, diversity of functional groups, α-diversity, and β-diversity (and its components) may be crucial to the holistic understanding of grazing exclusion effects on plant communities under drought conditions. Here, we investigated the response of these diversity measures to short-term sheep exclusion under severe drought episode in arid steppes of Alfa-grass (Stipa tenacissima) with a long evolutionary history of livestock grazing. Individual species responses were tested based on species occurrence and abundance in either grazed or grazing-excluded steppes, in addition, we used indicator species analysis to assess the strength of the association between plant species and management type. Likewise, α-diversity, abundance- and incidence-based β-diversity, as well as the functional groups’ diversities were quantified using Hill Numbers and compared between the two management types. Sheep grazing exclusion enabled the recovery of various Alfa-steppe indicator species and improved the size of regional species pool, overall α-diversity, and the diversity of therophytes. This management practice decreased the abundance-based β-diversity and the nestedness-resultant fraction of the incidence-based β-diversity at the local scale, while at the landscape scale increased the abundance-based β-diversity and its balanced variation fraction and reduced the incidence-based β-diversity and its turnover component. Furthermore, protection from grazing altered β-diversities scaling patterns by maintaining higher balanced variation in species abundance at large spatial scale and greater abundance-gradient in species composition at the fine-scale. Our results suggest that the implementation of short-term grazing exclusion in degraded arid steppes would be the appropriate management practice for vegetation restoration and plant diversity conservation during prolonged drought periods.

Preprint REVIEW | doi:10.20944/preprints201801.0189.v1

The Janus Face of NKT Cell Function in Autoimmunity and Infectious Diseases

Alessandra Torina, Giuliana Guggino, Marco Pio La Manna, Guido Sireci

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: microbes; autoimmunity; glycolipids,alpha-GalactosylCeramide; sulfatide; CD1d; NKT.

Online: 20 January 2018 (13:59:26 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202009.0251.v1

Influence of Different Light Regimes on the Mycoparasitic Activity and the Production of the Secondary Metabolite 6-Pentyl-α-Pyrone in Two Strains of Trichoderma Atroviride

Dubraska Moreno-Ruiz, Alessandro Fuchs, Kristina Missbach, Rainer Schuhmacher, Susanne Zeilinger

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Trichoderma atroviride; mycoparasitism; secondary metabolites; 6-pentyl-alpha-pyrone; Tmk3 MAP kinase; light; dark

Online: 11 September 2020 (08:49:15 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints202104.0353.v1

The Clampdown Effect: On The Expulsion of Super-Intelligence

Deep Bhattacharjee

Subject: Computer Science And Mathematics, Artificial Intelligence And Machine Learning Keywords: WEAK Clampdown Effect, STRONG Clampdown Effect, KARDASHEV Scale, ERROR Processing, EXTRAVAGENT Curiosity, SOFT Singularity, HARD Singularity, ERROR Approximation

Online: 13 April 2021 (12:58:00 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202105.0125.v1

A New Iterative Scheme for Approximation of Fixed Points of Suzuki's Generalized Nonexpansive Mappings

Shivam Rawat, Ramesh Chandra Dimri, Ayush Bartwal

Subject: Computer Science And Mathematics, Mathematics Keywords: Uniformly convex Banach space; Iteration process; Suzuki's generalized nonexpansive mapping; weak convergence; Strong convergence

Online: 7 May 2021 (09:05:49 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201905.0212.v1

Approximation of Fixed Points for Suzuki's Generalized Non-Expansive Mappings

Javid Ali, Faeem Ali, Puneet Kumar

Subject: Computer Science And Mathematics, Analysis Keywords: Suzuki's generalized non-expansive mappings; iterative schemes; fixed points; weak and strong convergence results; uniformly convex Banach spaces

Online: 16 May 2019 (10:54:50 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201803.0180.v1

Stochastic Resonance and Safe Basin of Single-Walled Carbon Nanotubes with Strongly Nonlinear Stiffness under Random Magnetic Field

Jia Xu, Chao Li, Yiran Li, CW Lim, Zhiwen Zhu

Subject: Chemistry And Materials Science, Nanotechnology Keywords: random magnetic field; safe basin; single-walled carbon nanotubes; stochastic resonance; strong nonlinearity

Online: 20 March 2018 (11:28:17 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202105.0171.v1

Bioactive Flavonoids from the Stem Bark of Cordia dichotoma Forst.: Identification, Docking and ADMET Studies

Nazim Hussain, Bibhuti Bhushan Kakoti, Mithun Rudrapal, Khomendra Kumar Sarwa, Ismail Celik, Emmanuel Ifeanyi Attah, Shubham Jagadish Khairnar, Soumya Bhattacharya, Ranjan Kumar Sahoo

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: C. dichotoma; Flavonoids; Antidiabetic; alpha-glucosidase, alpha-amylase, Docking; ADMET

Online: 10 May 2021 (11:02:24 CEST)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints202208.0061.v1

Epigenetics and Dysfunctional Energy Factors of Neurodegenerative Disease with Therapeutic Potential of H₂O₂ as Neuroprotective Agent

Sri Widyarti, Syahputra Wibowo, Akhmad Sabarudin, Intan Abhirama, Sutiman Bambang Sumitro

Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: alpha-synuclein; energy; H2O2; mitochondria; neurodegenerative disease

Online: 2 August 2022 (10:13:50 CEST)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints202207.0100.v1

From Minor Mutant to Dominance, the Evolution of SARS-CoV-2 Variants

Thomas Caspari

Subject: Biology And Life Sciences, Virology Keywords: omicron; alpha; delta; deltacron; recombination; RNA editing; intra-host variants; tropisms; ox-idative damage; Wuhan

Online: 6 July 2022 (15:27:32 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201901.0024.v3

Nikfar Domination Versus Others: Restriction, Extension Theorems and Monstrous Examples

Mohammadesmail Nikfar

Subject: Computer Science And Mathematics, Applied Mathematics Keywords: fuzzy graph, fuzzy bridge, α-strong edge, nikfar domination, dynamic networks.

Online: 14 May 2019 (09:50:12 CEST)

Show abstract| Download PDF| Share

The aim of this expository article is to present recent developments in the centuries-old discussion on the interrelations between several types of domination in graphs. However, the novelty even more prominent in the newly discovered simplified presentations of several older results. Domination can be seen as arising from real-world application and extracting classical results as first described by this article.The main part of this article, concerning a new domination and older one, is presented in a narrative that answers two classical questions: (i) To what extend must closing set be dominating? (ii) How strong is the assumption of domination of a closing set? In a addition, we give an overview of the results concerning domination. The problem asks how small can a subset of vertices be and contain no edges or, more generally how can small a subset of vertices be and contain other ones. Our work was as elegant as it was unexpected being a departure from the tried and true methods of this theory that had dominated the field for one fifth a century. This expository article covers all previous definitions. The inability of previous definitions in solving even one case of real-world problems due to the lack of simultaneous attentions to the worthy both of vertices and edges causing us to make the new one. The concept of domination in a variety of graphs models such as crisp, weighted and fuzzy, has been in a spotlight. We turn our attention to sets of vertices in a fuzzy graph that are so close to all vertices, in a variety of ways, and study minimum such sets and their cardinality. A natural way to introduce and motivate our subject is to view it as a real-world problem. In its most elementary form, we consider the problem of reducing waste of time in transport planning. Our goal here is to first describe the previous definitions and the results, and then to provide an overview of the flows ideas in their articles. The final outcome of this article is twofold: (i) Solving the problem of reducing waste of time in transport planning at static state; (ii) Solving and having a gentle discussions on problem of reducing waste of time in transport planning at dynamic state. Finally, we discuss the results concerning holding domination that are independent of fuzzy graphs. We close with a list of currently open problems related to this subject. Most of our exposition assumes only familiarity with basic linear algebra, polynomials, fuzzy graph theory and graph theory.

Preprint ARTICLE | doi:10.20944/preprints202011.0385.v1

mySORT: A Web Framework by using Deconvolution Approach to Estimating Immune Cell Composition from Complex Tissues

Shu-Hwa Chen, Bo-Yi Yu, Wen-Yu Kuo, Ya-Bo Lin, Sheng-Yao Su, I-Hsuan Lu, Chung-Yen Lin

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Cancer; Immunotherapy; Deconvolution; Alpha diversity; Beta diversity; Precision medicine; Microenvironment; Single-cell RNA sequencing

Online: 13 November 2020 (14:18:40 CET)

Show abstract| Download PDF| Share

Cancer immunotherapy reaches a remarkable achievement in various cancer types and brings new possibilities to improve cancer patients’ long-term survival. However, outcomes vary from case to case, and the present protocol benefits a small fraction of patients. One notable factor is the tumor microenvironment, especially the immune cell components, that may reflect the immune response's status quo on site. Thus, understanding the content of infiltrating immune cells in tumors is not only for research interesting but also a crucial subject toward precision medicine. We implement an algorithm for resolving relative proportions of twenty-one immune cell subclasses from a human tissue profiled transcriptome by microarray technology to reach the goal above. By selecting gene features and then adopting ?-Support Vector Regression, we can construct a deconvolution model and resolve the immune cell context. The excellent consistency between the estimated values and the correct immune-cell composition further demonstrates this approach provides a more natural alternative to revealing samples' immune cell content and reliable results like recent single-cell technologies. Based on this algorithm, the web-based deconvolution tool implemented named mySORT provides a user-friendly interface for estimating the immune cell content by uploading gene expression profiling. We also present comprehensive visualization 2D/3D plots in mySORT so that users can easily make a comparison between different samples. Finally, we synthesized pseudo-bulk expression data from single-cell transcriptomic datasets of 17 melanoma and 16 head and neck cancer patients. The deconvolution results of microarray-based data in the previous study and synthetic pseudo-bulk data all proved the excellent performance of mySORT. We believe that mySORT can help researchers in all fields easily understand complex immune microenvironment. The website of mySORT is freely accessible on https://symbiosis.iis.sinica.edu.tw/mySORT/.

Preprint REVIEW | doi:10.20944/preprints202007.0334.v1

The Role of Alpha-Synuclein And Other Parkinson’s Genes in Neurodevelopmental and Neurodegenerative Disorders

C. Alejandra Morato Torres, Zinah Wassouf, Faria Zafar, Danuta Sastre, Tiago Fleming Outeiro, Birgitt Schüle

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: alpha-synuclein; SNCA; PARK2; 22q11.2 deletion syndrome; autism spectrum disorders; neuronal development; Parkinson’s disease; neurodegeneration; synaptic dysfunction

Online: 15 July 2020 (11:36:30 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint REVIEW | doi:10.20944/preprints202312.0185.v1

Antibody Dependent Enhancement (ADE) of Infection into Macrophages Validates the Importance of HERV-K102 Particle Production for Pandemic Preparedness

Marian Laderoute

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: ADE, HERV-K102, HERV-K HML-2, immunosenescence, foamy macrophages, virus-anti-virus, pandemic preparedness, mRNA COVID-19 vaccines, alpha-fetoprotein antagonists, virus strategies, anti-viral, trained (innate) immunity

Online: 4 December 2023 (10:53:40 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202201.0174.v1

Pathological Relevance of Post-translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson’s Disease and Multiple System Atrophy

Berkiye Sonustun, Firat M Altay, Catherine Strand, Geshanthi Hondhamuni, Thomas T Warner, Hilal A Lashuel, Rina Bandopadhyay

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: alpha-synuclein; post-translational modifications; Parkinson’s disease; Multiple system atrophy; Lewy bodies; Lewy neurites; Glial cytoplasmic inclusions; phosphorylation; nitration; immunohistochemistry

Online: 12 January 2022 (14:31:13 CET)

Show abstract| Download PDF| Supplementary Files| Share

Working Paper ARTICLE

Quantum Optical Aspects of High-Harmonic Generation

Sándor Varró

Subject: Physical Sciences, Acoustics Keywords: generation of high harmonics; attosecond pulses; nonrelativistic quantum electrodynamics; strong laser field–matter interactions; quantum optics; nonclassical photon states

Online: 18 June 2021 (16:03:20 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201807.0096.v1

A Review on the Possible Existence of Strong Elementary Charge andits Nuclear Scale Applications

Satya Seshavatharam U.V, S. Lakshminarayana

Subject: Physical Sciences, Nuclear And High Energy Physics Keywords: Strong coupling constant, strong elementary charge, nuclear binding energy.

Online: 5 July 2018 (14:27:40 CEST)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints202312.1881.v2

Long Covid, the Gut, and Autoimmune Skin Diseases: A Novel Therapeutic Approach

Patrick W. Chambers, Shae E. Chambers

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: IFN-γ ; γ δ T cells; microbiome; d-mannose; TNF-α

Online: 28 December 2023 (14:34:12 CET)

Show abstract| Download PDF| Share

Preprint COMMUNICATION | doi:10.20944/preprints201906.0127.v1

Understanding Strong Coupling Constant, Nuclear Stability and Binding Energy with Three Atomic Gravitational Constants

Satya Seshavatharam U.V, S. Lakshminarayana

Subject: Physical Sciences, Nuclear And High Energy Physics Keywords: three atomic gravitational constants; strong coupling constant; nuclear stability; binding energy

Online: 13 June 2019 (13:40:18 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202107.0084.v1

Indication of Highly Correlated Electron Transport and Mott Insulator in Disordered Multilayer Ferritin Structures (DMFS)

Chris Rourk, Yunbo Huang, Minjing Chen, Cai Shen

Subject: Physical Sciences, Quantum Science And Technology Keywords: Ferritin; Quantum dots; Layer-by-layer deposition; Conductive atomic force microscopy; Strong correlations; mott insulator

Online: 5 July 2021 (10:07:03 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202102.0472.v1

Potential of Entomopathogenic Nematodes versus Alpha-cypermethrin Against Potato Tuber Moth, Phthorimaea operculella Zeller 1873 (Lep.: Gelechiidae) in Storage Conditions

Laleh Ebrahimi, Aziz Sheikhigarjan, Mehran Ghazavi

Subject: Biology And Life Sciences, Insect Science Keywords: EPNs; PTM; biological control; potato tuber; efficacy; alpha-cypermethrin

Online: 22 February 2021 (13:19:25 CET)

Show abstract| Download PDF| Share

Preprint COMMUNICATION | doi:10.20944/preprints202108.0117.v1

The α-Lipoic Acid Improves Hepatic Metabolic Dysfunctions in Acute Intermittent Porphyria: A Proof-of-Concept Study

Miriam Longo, Erika Paolini, Marica Meroni, Lorena Duca, Irene Motta, Anna L. Fracanzani, Elena Di Pierro, Paola Dongiovanni

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: AIP; PBGD; glucose metabolism; mitobiogenesis; alpha-lipoic acid

Online: 4 August 2021 (14:45:07 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints201804.0085.v3

Vertex Domination in Fuzzy Graphs

Mohammadesmail Nikfar

Subject: Computer Science And Mathematics, Computer Vision And Graphics Keywords: fuzzy graph; fuzzy bridge; fuzzy tree; $\alpha$-strong arc; vertex domination

Online: 5 May 2019 (12:20:38 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202104.0170.v1

Assessment of NF-κB Inhibitor (SN50) Effect on Adipose Tumor Necrosis Factor-Alpha and Angiotensinogen Secretion and Expression

Nasser M. Al-Dagheri, Assim A. Alfadda, Reem M. Sallam, Philip G. McTernan, Lotfi S. Bin Dahman

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: abdominal subcutaneous adipocytes; angiotensinogen; nuclear factor-kappa B; lipopolysaccharide; tumor necrosis factor-alpha

Online: 6 April 2021 (11:28:00 CEST)

Show abstract| Download PDF| Share

Central adiposity is one of the significant determinants of obesity-related hypertension risk, which may arise due to the abdominal fat depot's pathogenic inflammatory nature. Pro-inflammatory cytokines and adipokines up-regulation through nuclear factor-kappa B (NF-κB) activation in adipose tissue has been considered an essential function in the pathogenesis of obesity-related hypertension. This study aimed to ascertain the NF-κB inhibitor (SN50) effect on TNF-α and angiotensinogen (AGT) secretion and expression in mediating the anti-inflammatory effect through its impact on NF-κB activity in humans adipose tissue. Primary human adipocytes were isolated from 20 subjects among 10 overweight and 10 obese with and without hypertension and treated with 10ng/ml LPS in the presence and absence of NF-κB inhibitor, SN50 (50μg/ml). TNF-α secretion and NF-κB p65 activity were detected in supernatants extracted from cultured cells treated and untreated with LPS (10ng/ml) and SN50 (50μg/ml) using enzyme-linked immunosorbent assay (ELISA). The western blot technique detected the protein of NF-κB p65 and AGT. Gene expression of TNF-α and AGT was detected in cells and performed using quantitative real-time polymerase chain reaction (RT-PCR). Treatment of AbdSc adipocytes with LPS (10ng/ml) caused a significant increase in NF-κB p65 among overweight and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. In contrast, SN50-NF-κB inhibitor causes a reduction of NF-κB p65 in overweight (P= <0.001) and obese subjects with and without hypertension (P= 0.001) at 24 hours incubation. Treatment of AbdSc adipocytes with 10ng/ml LPS caused a significant increase in TNF-α secretion in overweight and obese subjects at all-time points (P= <0.001), whereas SN50 leads to a decrease in TNF-α secretion at 3 and 12 hours incubation. Treatment of AbdSc adipocytes with LPS (10ng/ml) caused increased TNF-α and AGT gene expression twofold compared with untreated cells, whereas, in the presence of SN50, it reduces mRNA AGT levels in both groups. Taken together, these adipokines with NF-κB activation may represent essential biomarkers to evaluate hypertension risk and to provide insight into the pathogenesis of obesity-related hypertension.

Preprint ARTICLE | doi:10.20944/preprints202201.0053.v1

Deciding on Optical Illusions: Reduced Alpha Power in Body Dysmorphic Disorder

Anastasios E. Giannopoulos, Ioanna Zioga, Konstantinos Kontoangelos, Panos Papageorgiou, Fotini Kapsali, Christos Ν. Capsalis, Charalabos Papageorgiou

Subject: Social Sciences, Behavior Sciences Keywords: body dysmorphic disorder; EEG; optical illusions; alpha oscillations

Online: 6 January 2022 (09:44:14 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202201.0103.v1

Significant Near Field Enhancement Over Large Volumes Around Metal Nanorods via Strong Coupling of Surface Lattice Resonances and Fabry-Pérot Resonance

Yunjie Shi, Yuming Dong, Degui Sun, Guangyuan Li

Subject: Physical Sciences, Optics And Photonics Keywords: Field enhancement; strong coupling; plasmonic-photonic coupling system; surface lattice resonance; Fabry-Pérot resonance.

Online: 10 January 2022 (12:05:33 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202101.0149.v1

Transcript Variants of Genes Involved in Neurodegeneration Are Differentially Regulated by the Apoe and Mapt Haplotypes

Sulev Koks, Abigail Pfaff, Vivien Bubb, John Quinn

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Apolipoprotein E (ApoE); microtubule associated protein (MAPT); synuclein alpha (SNCA); eQTL; TOMM40; KANSL1; mitochondria; Parkinson’s Progression Markers Initiative (PPMI)

Online: 8 January 2021 (11:45:19 CET)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints201909.0177.v1

Forest Diversity and Structure in the Amazonian Mountains Ranges of Southeastern Ecuador

Wilson Quizhpe, Angel Benítez, Jesus Muñoz, Klever Cuenca, Hernán Uvidia, Isau Huamantupa, Omar Cabrera

Subject: Biology And Life Sciences, Ecology, Evolution, Behavior And Systematics Keywords: alpha diversity; canonical correspondence; NMDS; Sandstones Forests; Terra firme Forests

Online: 17 September 2019 (03:48:02 CEST)

Show abstract| Download PDF| Supplementary Files| Share

1) Background: We analyzed the size structure, richness and diversity in eight permanent forest plots in the upper limit of the great Amazon basin located in the Ecuadorian parts of Cordilleras del Cóndor and Cutucú. Our hypothesis was that not all the forests of the eastern mountain ranges are homogeneous in characteristics, but rather present differences in their structure, richness and floristic diversity. In order to test this, our main objective was to classify the types of forests based on characteristics in diametric structure and species composition of the Amazonian forests of the eastern cordilleras in southern Ecuador, and also to determine the influence of critical edaphic-environmental and geomorphological factors. 2) Methods: Eight one-hectare permanent plots were installed in homogeneous and well-conserved forest stands. Four plots were located in the province of Zamora Chinchipe and four in the province of Morona Santiago. We identified and measured all trees> 10 cm at diameter breast height. For each plot, soil samples were taken, along with environmental and slope data. The multidimensional non-metric adjusted scaling (NMDS) was used to evaluate changes in climatic and geomorphological gradients. The relationship between the composition of the species at the plot level and the edaphoclimatic variables was tested using a canonical correspondence analysis (CCA). Finally, we modeled the change in species diversity (Fisher's alpha) in relation to the climatic gradients, altitudinal and geomorphological using a GLMM. 3) Results: Overall, we identified 517 species belonging to 76 families. We determined the existence of two different types of forest, the first one named Terra Firme, characterized by the presence of a larger number of species and individuals per plot, compared to the second type of forest, called Tepuy or Sandstones forest. Species richness was negatively correlated with soil phosphorus content and pH, mean annual temperature, annual precipitation and altitude. The CCA analysis showed differences in the species composition between the Terra Firme and Sandstone forests. The climatic seasonality and the concentration of cations in the soil influence the diversity of the Amazon forest communities of the southeastern cordilleras. The forests of Terra Firme, which are settled in more stable and nutrient-rich climatic areas, were more diverse. Sandstone forests are poor in nutrients and develop in areas with stronger seasonality

Preprint ARTICLE | doi:10.20944/preprints201812.0355.v2

Understanding Nuclear Binding Energy with Nucleon Mass Difference via Strong Coupling Constant and Strong Nuclear Gravity

Satya Seshavatharam U.V, S. Lakshminarayana

Subject: Physical Sciences, Nuclear And High Energy Physics Keywords: strong (nuclear) gravity; nuclear elementary charge; strong coupling constant; nuclear charge radius; beta stability line; nuclear binding energy; nucleon mass difference; Fermi’s weak coupling constant; Newtonian gravitational constant; deuteron; interaction range; super heavy elements

Online: 8 January 2019 (10:57:41 CET)

Show abstract| Download PDF| Share

With reference to electromagnetic interaction and Abdus Salam’s strong (nuclear) gravity, 1) Square root of ‘reciprocal’ of the strong coupling constant can be considered as the strength of nuclear elementary charge. 2) ‘Reciprocal’ of the strong coupling constant can be considered as the maximum strength of nuclear binding energy. 3) In deuteron, strength of nuclear binding energy is around unity and there exists no strong interaction in between neutron and proton.

G_{s} ≅ 3.32688 \times 10^{28} m^{3} {kg}^{- 1} \sec^{- 2}

being the nuclear gravitational constant, nuclear charge radius can be shown to be,

R_{0} ≅ \frac{2 G_{s} m_{p}}{c^{2}} ≅ 1.24 fm .

e_{s} ≅ (\frac{G_{s} m_{p}^{2}}{ℏ c}) e ≅ 4.716785 \times 10^{- 19} C

being the nuclear elementary charge, proton magnetic moment can be shown to be,

μ_{p} ≅ \frac{e_{s} ℏ}{2 m_{p}} ≅ \frac{e G_{s} m_{p}}{2 c} ≅ 1.48694 \times 10^{- 26} J {. T}^{- 1} .

α_{s} ≅ {(\frac{ℏ c}{G_{s} m_{p}^{2}})}^{2} ≅ 0.1153795

being the strong coupling constant, strong interaction range can be shown to be proportional to

\exp (\frac{1}{α_{s}^{2}}) .

Interesting points to be noted are: An increase in the value of

α_{s}

helps in decreasing the interaction range indicating a more strongly bound nuclear system. A decrease in the value of

α_{s}

helps in increasing the interaction range indicating a more weakly bound nuclear system. From

Z ≅ 30

onwards, close to stable mass numbers, nuclear binding energy can be addressed with,

{(B)}_{A_{s}} ≅ Z \times {(\frac{1}{α_{s}} + 1) + \sqrt{\sqrt{30 \times 31}}} (m_{n} - m_{p}) c^{2} \approx Z \times 19.66 MeV .

With further study, magnitude of the Newtonian gravitational constant can be estimated with nuclear elementary physical constants. One sample relation is,

(\frac{G_{N}}{G_{s}}) ≅ \frac{1}{2} {(\frac{m_{e}}{m_{p}})}^{10} [\sqrt{\frac{G_{F}}{ℏ c}} / (\frac{ℏ}{m_{e} c})]

where

G_{N}

represents the Newtonian gravitational constant and

G_{F}

represents the Fermi’s weak coupling constant. Two interesting coincidences are,

{(m_{p} / m_{e})}^{10} ≅ \exp (1 / α_{s}^{2})

and

2 G_{s} m_{e} / c^{2} ≅ \sqrt{G_{F} / ℏ c} .

Preprint ARTICLE | doi:10.20944/preprints202008.0316.v1

Next-Generation Multimodality of Nanomedicine Therapy: Folic Acid Conjugated Copolymer and Folate Receptor Interactions Disrupt Receptor Functionality Resulting in Dual Therapeutic Anti-Cancer Potential in Triple-Negative Breast Cancer

Alexandria DeCarlo, Cecile Malardier-Jugroot, Myron R Szewczuk

Subject: Chemistry And Materials Science, Nanotechnology Keywords: nanoparticles; FA-DABA-SMA; drug delivery systems; folic acid receptor alpha; intracellular disruptions; invasion and migration; breast cancer

Online: 14 August 2020 (09:49:17 CEST)

Show abstract| Download PDF| Share

The development of a highly specific drug delivery system (DDS) for anti-cancer therapeutics is an area of intense research focus. Chemical engineering of a “smart” DDS to specifically target tumor cells has gained interest, designed for safer, more efficient, and effective use of chemotherapeutics for the treatment of cancer. However, the selective targeting and choosing the critical cancer surface biomarker are essential for targeted treatments to work. The folic acid receptor alpha (FRalpha) has gained popularity as a potential target in triple-negative breast cancer (TNBC). We have previously reported on a functionalized folic acid (FA)-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) that has the essential features for efficient “smart” DDS. This biocompatible DDS self-assembles in a pH-dependent manner, providing stimuli-responsive, active targeting, extended-release of hydrophobic chemotherapeutic agents, and can effectively penetrate the inner core of 3-dimensional cancer spheroid models. The empty FA-DABA-SMA decreased spheroid volume, revealing a previously unknown mechanism of action. Upon further investigation, a size- and shape-dependent interaction FA-DABA-SMA with FR reduced the expression of p53, the product of the highly mutated TP53 gene, and additional oncogenic c-Myc and STAT3 proteins. Here, we investigated how this copolymer influences FR behavior and disrupting the receptor’s functions. Results indicate that FA-DABA-SMA increases FR expression levels in breast MDA MB-231 cancer cells and disrupting FR signaling by the reduction in HES1 and NOTCH1 protein expression levels. Also, FA-DABA-SMA induces apoptosis and further causes a change in the morphology of the MDA MB-231 cells, as well as significantly reduces their ability to migrate in a Scratch wound assay. Collectively, these findings provide a novel insight into the functionalized FA-DABA-SMA copolymer. The 350 kDa and 20 kDa copolymers actively target FRα to initialize internationalization. However, only the large size and sheet-shaped 350 kDa copolymers disrupt FRα signaling. The significance of these novel findings reveals the intracellular activity of the copolymer that is critically dependent on the size and structural shape. This report offers novel therapeutic insight into a dual mechanism of FA-DABA-SMA copolymer for its therapeutic potential for the treatment of cancer.

Preprint ARTICLE | doi:10.20944/preprints202205.0184.v1

Amyloid Precursor Protein, Alpha-, Beta- and Gamma-Secretases Expression in Penumbra Cells after Photothrombotic Stroke. Evaluation of the Neuroprotective Effect of Secretase Inhibitors

Svetlana Sharifulina, Valeria Guzenko, Alexandr Logvinov, Andrey Khaitin, Yuliya Kalyuzhnaya, Natalia Dobaeva, Yan Li, Lei Chen, Вin He, Svetlana Demyanenko

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: amyloid precursor protein; photothrombotic stroke; ischemia; alpha-secretase; beta-secretase; gamma-secretase

Online: 13 May 2022 (08:39:09 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints201809.0195.v1

Random Fixed Point Theorems for Generalized Random α-ψ-contractive Mappings with Applications to Stochastic Differential Equation

Chayut Kongban, Poom Kumam, Juan Martinez-Moreno

Subject: Computer Science And Mathematics, Analysis Keywords: random fixed point, random $\alpha-$admissible with respect to $\eta$, generalized random $\alpha-\psi-$contractive mapping.

Online: 11 September 2018 (11:52:25 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202205.0280.v1

Analysis of the Structural Protein Effects Caused by the PURA p.Phe233del Mutation Associated to Cognitive Developmental Delay Using Artificial Intelligence and Hybrid Quantum Mechanics-Molecular Mechanics Modelling

Juan Javier Lopez-Rivera, Luna Rodríguez-Salazar, Alejandro Soto-Ospina, Carlos Estrada-Serrato, David Serrano, Henry Mauricio Chaparro-Solano, Olga Londoño, Paula A. Rueda, Geraldine Ardila, Andrés Villegas-Lanau, Marcela Godoy-Corredor, Mauricio Cuartas, Jorge I. Vélez, Oscar M. Vidal, Mario A. Isaza-Ruget, Mauricio Arcos-Burgos

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: purine-rich element binding protein A gene; PURA; MIM: 600473; transcriptional activator protein Pur-alpha; cognitive developmental delay; mental retardation; Mutation c.697_699del p.Phe233del

Online: 20 May 2022 (16:58:04 CEST)

Show abstract| Download PDF| Share

A whole-exome capture and next-generation sequencing applied to an 11 y/o patient with a clinical history of congenital hypotonia, generalized motor and cognitive neurodevelopmental delay, severe cognitive deficit, without any identifiable Syndromic pattern, and to her parents, disclosed a de novo heterozygous pathogenic mutation, c.697_699del p.Phe233del (rs786204835)(ACMG classification PS2, PM1, PM2, PP5), harbored in the PURA gene (MIM*600473) (5q31.3), associated to Autosomal Dominant Mental Retardation 31 (MIM # 616158). We used the significant improvement in the accuracy of protein structure prediction recently implemented in AlphaFold that incorporates novel neural network architectures and training procedures based on the evolutionary, physical, and geometric constraints of protein structures. The wild-type (WT) sequence and the mutated one, missing the Phe233, were reconstructed. The predicted local Distance Difference Test (lDDT) for the PURA WT and the PURA-Phe233del showed that the occurrence of the Phe233del affects between 220-320 amino acids. The distortion in the PURA structural confor-mation in the ~5Å surrounding area after the p.Phe233del produces a conspicuous disruption of the repeat III, where the DNA and RNA helix unwinding capability occurs. PURA Protein-DNA Docking corroborated these results in silico Analysis that showed a loss of the contact of the PURA-Phe233del III repeat domain model with the DNA. Together, i) the energetic and stereochemical, ii) the hydropathic indices and polarity surfaces, and iii) the hybrid Quantum Mechanics-Molecular Mechanics (QM-MM) analyses of the PURA molecular models demarcate at the atomic resolution the specific surrounding region affected by these mutations and paves the way for future cell-based functional analysis. To the best of our knowledge, this is the first report of a de novo mutation underpinning a PURA syndrome in a Latin American patient and highlights the importance of predicting the molecular effects in protein structure using artificial intelligence algorithms and molecular and atomic resolution stereochemical analyses.

Preprint ARTICLE | doi:10.20944/preprints202005.0001.v1

Using High-Content Screening Technology as a Tool to Generate Single-Cell Patient-Derived Gene-Corrected Isogenic iPS Clones for Parkinson’s Disease Research

Peter A. Barbuti, Paul M. Antony, Bruno F.R. Santos, François Massart, Gérald Cruciani, Claire M. Dording, Jonathan Arias, Jens C. Schwamborn, Rejko Krüger

Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: CRISPR-Cas9; high-content screening (HCS); fluorescent-activated cell sorting (FACS); Parkinson's disease (PD); patient-derived iPS; single-cell clones; isogenic cell lines; SNCA; alpha-synuclein; A30P

Online: 2 May 2020 (11:20:20 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints202104.0137.v1

Gross Alpha and Gross Beta Activity Concentrations in Dust Fraction of Urban Surface Deposited Sediment in Russian Cities

Mohamed Y. Hanfi, Andrian A. Seleznev, Ilia Yarmoshenko

Subject: Environmental And Earth Sciences, Atmospheric Science And Meteorology Keywords: urban surface deposited sediments (USDS); gross alpha activity (GA); gross beta activity (GB); dust

Online: 5 April 2021 (13:00:40 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202111.0409.v1

Floquet Spectral Almost Periodic Modulation of Massive Finite and Infinite Strongly Coupled Arrays: Dense Massive MIMO, Intelligent Surfaces, 5G and 6G Applications

Hamdi Bilel, Aguili Taoufik

Subject: Engineering, Electrical And Electronic Engineering Keywords: Floquet analysis; MoM method; Almost periodic antenna arrays; Fourier analysis; strong mutual coupling; Dense massive MIMO; MM and THz waves; 5G and 6G applications

Online: 22 November 2021 (15:11:58 CET)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints202105.0002.v1

The Catecholaldehyde Hypothesis for the Pathogenesis of Catecholaminergic Neurodegeneration: What We Know and What We Don’t Know

David S Goldstein

Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Catecholaldehyde; DOPAL; Autotoxicity; Monoamine Oxidase; Dopamine; Alpha-Synuclein

Online: 3 May 2021 (09:08:57 CEST)

Show abstract| Download PDF| Share

3,4-dihydroxyphenylacetaldehyde (DOPAL) is the focus of the catecholaldehyde hypothesis for the pathogenesis of Parkinson disease and other Lewy body diseases. The catecholaldehyde is produced via oxidative deamination catalyzed by monoamine oxidase (MAO) acting on cytoplasmic dopamine. DOPAL is autotoxic, in that it can harm the same cells in which it is produced. Normally DOPAL is detoxified by aldehyde dehydrogenase (ALDH)-mediated conversion to 3,4-dihydroxyphenylacetic acid (DOPAC), which rapidly exits the neurons. Genetic, environmental, or drug-induced manipulations of ALDH that build up DOPAL promote catecholaminergic neurodegeneration. A concept derived from the catecholaldehyde hypothesis imputes deleterious interactions between DOPAL and the protein alpha-synuclein (S), a major component of Lewy bodies. DOPAL potently oligomerizes S, and S oligomers impede vesicular and mitochondrial functions, shifting the fate of cytoplasmic dopamine toward MAO-catalyzed formation of DOPAL—destabilizing vicious cycles. Direct and indirect effects of DOPAL and of DOPAL-induced misfolded proteins could “freeze” intra-neuronal reactions, plasticity of which is required for neuronal homeostasis. The extent to which DOPAL toxicity is mediated by interactions with S, and vice versa, are poorly understood. Because of numerous secondary effects such as augmented spontaneous oxidation of dopamine by MAO inhibition, there has been insufficient testing of the catecholaldehyde hypothesis in animal models. The clinical pathophysiological significance of genetics, emotional stress, environmental agents, and interactions with numerous proteins relevant to the catecholaldehyde hypothesis are matters for future research. The imposing complexity of intra-neuronal catecholamine metabolism seems to require a computational modeling approach to elucidate clinical pathogenetic mechanisms and devise pathophysiology-based, individualized treatments.

Preprint ARTICLE | doi:10.20944/preprints202003.0278.v2

Global in Time Existence of Strong Solution to 3D Navier-Stokes Equations

Abdelkerim Chaabani

Subject: Computer Science And Mathematics, Applied Mathematics Keywords: Navier Stokes; strong solution; global existence

Online: 24 March 2020 (03:33:43 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201810.0053.v2

A Large Nuclear Gravitational Constant and its Universal Applications

Satya Seshavatharam U.V, S. Lakshminarayana

Subject: Physical Sciences, Nuclear And High Energy Physics Keywords: Strong nuclear gravity, nuclear elementary charge, strong coupling constant, nuclear stability range, binding energy of isotopes, magic proton numbers.

Online: 16 October 2018 (15:28:20 CEST)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints202212.0276.v1

Rethinking the Paradoxical Increase in Endogenous Glucose Production in Response to Metformin: Should We Retain the Glucagon Antagonistic Effect of the Drug?

Jabeur Methnani, Taieb Ach, Aymen El Hraiech, Imed Latiri, Ali Bouslama, Monia Zaouali, Asma omezzine, Ezdine Bouhlel

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Biguanides; Antihyperglycemic agents; Liver alpha-cell axis; gluconeogenesis; Protein metabolism; insulin sensitivity

Online: 15 December 2022 (08:37:28 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202105.0743.v1

Applications of PERALS-Alpha Spectrometry for the Investigation of Radionuclides in Water Samples

Markus Raymond Zehringer, Franziska Kammerer, Anja Pregler

Subject: Physical Sciences, Acoustics Keywords: PERALS; alpha spectrometry; Polonium; Radon; Radium; Radiostrontium; Thorium; Uranium; Actinides

Online: 31 May 2021 (11:16:23 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202104.0413.v2

Total Face Irregularity Strength of Type (Alpha, Beta, Gamma) of Grid Graphs

Abdul Aleem Mughal, Raja Noshad Jamil

Subject: Computer Science And Mathematics, Computer Vision And Graphics Keywords: Total Face labeling of type (Alpha, Beta, Gamma); Total face irregularity strength; artesian product of path graphs; Graph Labeling; Graph theory

Online: 21 April 2021 (12:46:29 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201804.0119.v1

Vertex Domination in t-Norm Fuzzy Graphs

Mohammadesmail Nikfar

Subject: Computer Science And Mathematics, Computer Vision And Graphics Keywords: t-norm Fuzzy graph; t-norm; fuzzy tree; bridge; α-strong edges; vertex domination

Online: 10 April 2018 (08:41:33 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201811.0324.v1

Associations between the Duration and Frequency of Sedentary Bouts and Adiposity in Elderly Community-Dwelling Women

Jana Pechová, Jana Pelclová, Aleš Gába, Izabela Zając-Gawlak, Lenka Tlučáková, Jan Dygrýn, Zuzana Svozilová, Hana Lepková

Subject: Social Sciences, Behavior Sciences Keywords: Adipose tissue, Adiposity, Sedentary bouts, Alpha sedentary, Elderly women

Online: 14 November 2018 (08:09:04 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201810.0283.v1

Geomorphology and Altitude Effects on Diversity and Structure of Vanishing Montane Forest of Southern Ecuador

Omar Cabrera, Angel Benítez, Nixon Cumbicus, Carlos Naranjo, Pablo Ramón, Fani Tinitana, Adrián Escudero

Subject: Biology And Life Sciences, Forestry Keywords: alpha diversity; beta diversity; floristic arrangement; geological landscapes; geomorphology; Ecuador; mountain forests

Online: 15 October 2018 (06:19:16 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints201810.0391.v1

Wheat ATI CM3, CM16 and 0.28 Allergens Produced in Pichia Pastoris Display a Different Eliciting Potential in Food Allergy to Wheat

Silvio Tundo, Roberta Lupi, Mickael Lafond, Thierry Giardina, Colette Larré, Sandra Denery-Papini, Martine Morisset, Raviraj Kalunke, Francesco Sestili, Stefania Masci

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: wheat; alpha-amylase/trypsin inhibitor; heterologous expression; Pichia pastoris; allergy

Online: 17 October 2018 (17:15:23 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints202201.0442.v1

Global Powerful Alliance in Strong Neutrosophic Graphs

Henry Garrett

Subject: Computer Science And Mathematics, Applied Mathematics Keywords: Modified Neutrosophic Number; Global Powerful Alliance; R-Regular-Strong

Online: 28 January 2022 (15:09:54 CET)

Show abstract| Download PDF| Share

New setting is introduced to study the global powerful alliance. Global powerful alliance is about a set of vertices which are applied into the setting of neutrosophic graphs. Neighborhood has the key role to define this notion. Also, neighborhood is defined based on strong edges. Strong edge gets a framework as neighborhood and after that, too close vertices have key role to define global powerful alliance based on strong edges. The structure of set is studied and general results are obtained. Also, some classes of neutrosophic graphs excluding empty, path, star, and wheel and containing complete, cycle and r-regular-strong are investigated in the terms of set, minimal set, number, and neutrosophic number. Neutrosophic number is used in this way. It’s applied to use the type of neutrosophic number in the way that, three values of a vertex are used and they’ve same share to construct this number. It’s called “modified neutrosophic number”. Summation of three values of vertex makes one number and applying it to a set makes neutrosophic number of set. This approach facilitates identifying minimal set and optimal set which forms minimal-global-powerful-alliance number and minimal-global-powerful-alliance-neutrosophic number. Two different types of sets namely global-powerful alliance and minimal-global-powerful alliance are defined. Global-powerful alliance identifies the sets in general vision but minimal-global-powerful alliance takes focus on the sets which deleting a vertex is impossible. Minimal-global-powerful-alliance number is about minimum cardinality amid the cardinalities of all minimal-global-powerful alliances in a given neutrosophic graph. New notions are applied in the settings both individual and family. Family of neutrosophic graphs has an open avenue, in the way that, the family only contains same classes of neutrosophic graphs. The results are about minimal-global-powerful alliance, minimal-global-powerful-alliance number and its corresponded sets, minimal-global-powerful-alliance-neutrosophic number and its corresponded sets, and characterizing all minimal-global-powerful alliances, minimal-t-powerful alliance, minimal-t-powerful-alliance number and its corresponded sets, minimal-t-powerful-alliance-neutrosophic number and its corresponded sets, and characterizing all minimal-t-powerful alliances. The connections amid t-powerful-alliances are obtained. The number of connected components has some relations with this new concept and it gets some results. Some classes of neutrosophic graphs behave differently when the parity of vertices are different and in this case, cycle, and complete illustrate these behaviors. Two applications concerning complete model as individual and family, under the titles of time table and scheduling conclude the results and they give more clarifications and closing remarks. In this study, there’s an open way to extend these results into the family of these classes of neutrosophic graphs. The family of neutrosophic graphs aren’t study deeply and with more results but it seems that analogous results are determined. Slight progress is obtained in the family of these models but there are open avenues to study family of other models as same models and different models. There’s a question. How can be related to each other, two sets partitioning the vertex set of a graph? The ideas of neighborhood and neighbors based on strong edges illustrate open way to get results. A set is global powerful alliance when two sets partitioning vertex set have uniform structure. All members of set have more amount of neighbors in the set than out of set and reversely for non-members of set with less members in the way that the set is simultaneously t-offensive and(t-2)-defensive. A set is global if t=0. It leads us to the notion of global powerful alliance. Different edges make different neighborhoods but it’s used one style edge titled strong edge. These notions are applied into neutrosophic graphs as individuals and family of them. Independent set as an alliance is a special set which has no neighbor inside and it implies some drawbacks for these notions. Finding special sets which are well-known, is an open way to purse this study. Special set which its members have only one neighbor inside, characterize the connected components where the cardinality of its complement is the number of connected components. Some problems are proposed to pursue this study. Basic familiarities with graph theory and neutrosophic graph theory are proposed for this article.

Preprint ARTICLE | doi:10.20944/preprints202001.0020.v2

4G Model of Final Unification - A Very Brief Report

U. V. S. Seshavatharam, S. Lakshminarayana

Subject: Physical Sciences, Particle And Field Physics Keywords: four gravitational constants; strong nuclear charge; electroweak fermion; Hadron mass generator; super symmetry

Online: 21 January 2020 (03:30:26 CET)

Show abstract| Download PDF| Share

Preprint CONCEPT PAPER | doi:10.20944/preprints201809.0209.v1

Paths for Improving Bevacizumab Available in 2018: The ADZT Regimen for Better Glioblastoma Treatment

Richard Kast

Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: ADZT regimen; apremilast; bevacizumab; cAMP; dapsone; glioblastoma; telmisartan; TNF-alpha; zonisamide

Online: 12 September 2018 (03:54:33 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201910.0241.v1

Coupled Stratospheric Chemistry-Meteorology Data Assimilation. Part II: Weak and Strong Coupling

Richard Ménard, Pierre Gauthier, Yves Rochon, Alain Robichaud, Jean de Grandpré, Yan Yang, Cécilien Charette, Simon Chabrillat

Subject: Environmental And Earth Sciences, Atmospheric Science And Meteorology Keywords: coupled chemistry-meteorology data assimilation; weak and strong data assimilation coupling; Canadian Quick Covariance method (CQC); assimilation of MIPAS temperature observations; ozone-temperature cross-covariance; tracer-wind 4D-Var assimilation

Online: 21 October 2019 (05:09:58 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints202203.0090.v1

Strong Coupling between A Single Quantum Emitter and a Plasmonic Nanoantenna on a Metallic Film

Shun Cao, Yuwei Sun, Zhenchao Liu, Sailing He

Subject: Physical Sciences, Optics And Photonics Keywords: strong coupling; nanoantenna; single quantum dot

Online: 7 March 2022 (07:49:51 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202009.0391.v1

Alpha-glucosidase and Alpha-amylase Inhibitory Activities, Molecular Docking and Antioxidant Capacities of Salvia Aurita Constituents

Ninon G.E.R Etsassala, Jelili A. Badmus, Jeanine L. Marnewick, Felix Nchu, Ahmed A. Hussein

Subject: Chemistry And Materials Science, Medicinal Chemistry Keywords: Diabetes mellitus; oxidative stress; alpha-glucosidase; alpha-amylase; Salvia aurita; abietane diterpenes

Online: 17 September 2020 (09:03:16 CEST)

Show abstract| Download PDF| Share

Diabetes mellitus (DM) is one of the most dangerous metabolic diseases with high rate of mortality worldwide. It is well known that insulin resistance and deficiency in insulin production from pancreatic β-cells are the main characteristic of DM. Due to the detrimental side effects of the current treatment, there is a considerable need to develop new effective antidiabetic drugs, especially alpha-glucosidase and alpha-amylase inhibitors with lesser adverse effects. These inhibitors are known to be directly involved in the delay of carbohydrate digestion, resulting in a reduction of glucose absorption rate and consequently reduce the post-prandial raise of plasma glucose, which can reduce the risk of long-term diabetes complications. Hence, natural products are well-known sources for the discovery of new scaffold for drugs discovery, including new antidiabetic drugs. The phytochemical investigation of Salvia aurita collected from Hogobach pass, Eastern Cape, South Africa (SA), yielded four known abietane diterpenes namely carnosol (1), rosmanol (2), 7-methoxyrosmanol (3), 12-methoxycarnosic acid (4) and one flavonoid named 4,7-dimethylapigenin (5). Structural characterization of these isolated compounds was conducted using 1 and 2D NMR, in comparison with reported spectroscopic data. These compounds are reported for the first time from S. aurita. The biological evaluation of the isolated compound against alpha-glucosidase exhibited strong inhibitory activities for 3 and 2 with IC50 values of 4.2 ± 0.7 and 16.4 ± 1.1 µg/mL respectively, while 4 and 1 demonstrated strong alpha-amylase inhibitory activity amongst the isolated compounds with IC50 of 16.2 ± 0.3 and 19.8 ± 1.4 µg/mL. Molecular docking analysis confirms strong inhibitory activity of 3 against alpha-glucosidase. Additionally, excellent antioxidant capacities were displayed by 2, 1 and 3 respectively as ORAC (25789.9 ± 10.5; 23961.8 ± 14.1; 23939.3 ± 2.4) µM TE/g; 1 and 2 as FRAP (3917.8 ± 2.1; 1522.3 ± 0.9) µM AAE/g; 5 and 2 as TEAC (3190.4 ± 2.8; 2055.0 ± 2.6) µM TE/g. The methanolic extract of S. aurita is a rich source of abietane diterpenes with excellent antioxidant and anti-diabetic activities that can be useful to modulate oxidative stress, and might possibly be excellent candidates for the management of diabetes. This is the first scientific report on the phytochemical isolation and biological evaluation of alpha-glucosidase and alpha-amylase inhibitory activities of Salvia aurita.

Preprint ARTICLE | doi:10.20944/preprints202011.0526.v1

Effect of α-Hemolysin Producing E. coli in Two Different Mouse Strains in a DSS Model of Inflammatory Bowel Disease

Hengameh Chloé Mirsepasi-Lauridsen, Carsten Struve, Andreas Munk Petersen, Karen Angeliki Krogfelt

Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: inflammatory-bowel-disease; Sigirr -/- mice; C57BL/6-mice; Escherichia coli; alpha hemolysin

Online: 20 November 2020 (09:14:48 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201911.0134.v1

Implications and Applications of Fermi Scale Quantum Gravity

U.V.S. Seshavatharam, S. Lakshminarayana

Subject: Physical Sciences, Nuclear And High Energy Physics Keywords: four gravitational constants; compound reduced Planck’s constant; nuclear elementary charge; strong coupling constant; nuclear stability and binding energy; quark masses

Online: 12 November 2019 (16:53:07 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201912.0374.v1

Elucidating Binding Sites and Affinities of ERα Agonist and Antagonist to Human Alpha-Fetoprotein by in silico Modeling and Point Mutagenesis

Nurbubu T. Moldogazieva, Daria S. Ostroverkhova, Nikolai N. Kuzmich, Vladimir V. Kadochnikov, Alexander A. Terentiev, Yuri B. Porozov

Subject: Biology And Life Sciences, Biophysics Keywords: alpha-fetoprotein; estrogens; selective estrogen receptor modulators; homology-based modeling; molecular docking; protein-ligand interaction; amino acid substitutions

Online: 29 December 2019 (08:08:23 CET)

Show abstract| Download PDF| Share

Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting variety of hydrophobic ligands including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth and this can be attributed to its estrogen-binding ability. Despite AFP has long been investigated, its three-dimensional (3D) structure has not been experimentally resolved and molecular mechanisms underlying AFP-ligand interaction remain obscure. In our study we constructed homology-based 3D model of human AFP (HAFP) with the purpose to perform docking of ERα ligands, three agonists (17β-estradiol, estrone and diethylstilbestrol) and three antagonists (tamoxifen, afimoxifene and endoxifen) into the obtained structure. Based on ligand docked scoring function, we identified three putative estrogen- and antiestrogen-binding sites with different ligand binding affinities. Two high-affinity sites were located in (i) a tunnel formed within HAFP subdomains IB and IIA and (ii) opposite side of the molecule in a groove originating from cavity formed between domains I and III, while (iii) the third low-affinity site was found at the bottom of the cavity. 100 ns MD simulation allowed studying their geometries and showed that HAFP-estrogen interactions occur due to van der Waals forces, while both hydrophobic and electrostatic interactions were almost equally involved in HAFP-antiestrogen binding. MM/GBSA rescoring method estimated binding free energies (ΔG_bind) and showed that antiestrogens have higher affinities to HAFP as compared to estrogens. We performed in silico point substitutions of amino acid residues to confirm their roles in HAFP-ligand interactions and showed that Thr132, Leu138, His170, Phe172, Ser217, Gln221, His266, His316, Lys453, and Asp478 residues along two disulfide bonds, Cys224-Cys270 and Cys269-Cys277 have key roles in both HAFP-estrogen and HAFP-antiestrogen binding. Data obtained in our study contribute to understanding mechanisms underlying protein-ligand interactions and anti-cancer therapy strategies based on ER-binding ligands.

Preprint ARTICLE | doi:10.20944/preprints202110.0117.v1

HIF-alpha Activation Impacts Macrophage Function During Murine Leishmania major Infection

Manjunath Bettadapura, Hayden Roys, Anne Bowlin, Gopinath Venugopal, Charity L. Washam, Lucy Fry, Steven Murdock, Humphrey Wanjala, Stephanie D. Byrum, and Tiffany Weinkopff

Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Leishmania; leishmaniasis; macrophages; HIF-alpha

Online: 7 October 2021 (11:00:12 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202206.0274.v1

α-amylase Inhibition Activity of Phytoconstituents Present in the Roots Of Cyclea peltata-An in-silico and in-vitro Investigation

Gandhimathi R., Binoy Varghese Cheriyan, Deevan Paul A., Saravanakumar A., Lakshmanan G.

Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Cyclea peltata; Diabetes Mellitus; Docking; Schrodinger; Alpha amylase; Inhibition

Online: 20 June 2022 (14:33:11 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202001.0295.v1

Suppression of Hepatocyte Nuclear Factor 4 Alpha by Long-Term Infection of Hepatitis B Virus Contributes to Tumor Cell Proliferation

Soree Park, Yea Na Ha, Mehrangiz Dezhbord, Ah Ram Lee, Eun-Sook Park, Yong Kwang Park, Juhee Won, Na Yeon Kim, Soo Yeun Choo, Jae Jin Shin, Chang Hyun Ahn, Kyun-Hwan Kim

Subject: Biology And Life Sciences, Virology Keywords: Hepatitis B virus; hepatocyte nuclear factor 4 alpha; long-term infection; ERK signaling pathway

Online: 25 January 2020 (15:25:57 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201912.0391.v1

4G Model of Fractional Charge Strong-Weak Super Symmetry

U.V.S. Seshavatharam, S. Lakshminarayana

Subject: Physical Sciences, Particle And Field Physics Keywords: four gravitational constants; super symmetry; strong charge; strong coupling constant; quark fermions; quark bosons; fluons; bluons; baryons; mesons

Online: 30 December 2019 (04:15:13 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints201911.0398.v2

Hypothetical Role of Large Nuclear Gravity in Understanding the Significance and Applications of the Strong Coupling Constant in the Light of Up and Down Quark Clusters

U.V.S Seshavatharam, S. Lakshminarayana

Subject: Physical Sciences, Nuclear And High Energy Physics Keywords: large nuclear gravity; strong coupling constant; nuclear stability; nuclear binding energy; free nucleons; active nucleons; magic numbers; up and down Quark clusters

Online: 4 December 2019 (04:48:31 CET)

Show abstract| Download PDF| Supplementary Files| Share

Preprint REVIEW | doi:10.20944/preprints202403.1866.v1

Proximate Causes of Ageing Are Likely Evolutionarily Bound and Appropriate Countermeasure Design Requires New Approaches

Luke Slade, Timothy Etheridge, Nathaniel Szewczyk

Subject: Biology And Life Sciences, Aging Keywords: Hyperfunction; C. elegans; ageing; gene optimisation; healthspan

Online: 29 March 2024 (15:55:49 CET)

Show abstract| Download PDF| Share

Understanding mechanisms of ageing remains a complex challenge for biogerontologists, but recent adaptations of evolutionary ageing theories offer a compelling lens in which to view both age-related molecular and physiological deterioration. Ageing is commonly associated with a progressive loss of biochemical processes and degeneration of molecular material, however, the mechanisms of diminishing function are not simply a result of aberrant expression of these pathways. Natural selection pressures are at their highest in youthful periods to select genes advantageous to maximising reproductive capacity. After sexual maturation, selective pressure diminishes, subjecting individuals to maladaptive pleiotropic gene function once beneficial for developmental growth, but pathogenic later in life. Due to this selective ‘shadowing’ in ageing, mechanisms to counter hyperfunctional genes are unlikely to evolve within a given species. These genetic ‘run-on’ programmes are not dysfunctional per se and, in fact, remain highly robust. Thus, interventions capable of optimising gene function during the ageing process represent as attractive therapeutic modalities. Caenorhabditis elegans offers a unique model to explore high-throughput screening of interventions to combat hyperfunctional pathways involved in ageing. However, the majority of research to date employ whole-life vs late-life pathway manipulation of developmental/growth-related systems to claim ageing attenuation, despite significant impairments in early-life fitness and discordance with healthspan. Here, we discuss data supporting hyperfunctional changes at a global molecular and functional level in C. elegans, and how classical lifespan-extension mutants alter these dynamics. We later discuss the relevance of such mutant models for exploring mechanisms of ageing, highlighting that post-reproductive gene manipulation represents a far more translatable approach for C. elegans research not routed within pleiotropic constraints. More so, lifespan has become a routine readout for quantifying ‘ageing’, however, we make the argument that a compression of gerospan vs lifespan extension is a more meaningful goal for anti-ageing regimes with current knowledge. Similarly, mechanisms governing lifespan are distinct from those regulating health, and slowing senescent pathology accumulation appears more applicable for the abstraction to human ageing.

Preprint ARTICLE | doi:10.20944/preprints202011.0428.v1

On the Fourth Coefficient of the Inverse of a Starlike Function of Positive Order

Toshiyuki Sugawa, Li-Mei Wang

Subject: Computer Science And Mathematics, Algebra And Number Theory Keywords: starlike function of order $\alpha$; inverse function; coefficient estimates

Online: 16 November 2020 (15:08:35 CET)

Show abstract| Download PDF| Share

Preprint REVIEW | doi:10.20944/preprints202404.0460.v1

Quantum Correlation Enhanced Optical Imaging

Siddhant Vernekar, Jolly Xavier

Subject: Physical Sciences, Optics And Photonics Keywords: Quantum photonics, Quantum imaging, Quantum correlations, Quantum key distribution, Quantum sensing

Online: 8 April 2024 (13:53:54 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202112.0453.v1

Detection of Novel Biomarkers in Saliva of Rheumatoid Arthritis Model Mice by Proteomics and Pathological Analysis

Wakako Sakaguchi, Juri Saruta, Shinya Fuchida, Yuko Yamamoto, Masahiro To, Tomoko Shimizu, Mayumi Yakeishi, Keiichi Tsukinoki

Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: anti-citrullinated protein antibody (ACPA); alpha-1-antitrypsin (A1AT); DBA/1JJmsSlc mice Proteome analysis; rheumatoid arthritis (RA)

Online: 28 December 2021 (14:44:54 CET)

Show abstract| Download PDF| Supplementary Files| Share

Preprint COMMUNICATION | doi:10.20944/preprints202210.0383.v2

Pioneering Organelle Structural Biology: Golgi Apparatus Dysfunction in Parkinson’s Disease, Neurodevelopmental Disorders, and Cancer

Daniel Gómez

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: structural biology; organelles; Golgi Apparatus (GA); Parkinson’s disease (PD); cryo-ET; alpha-synuclein; neurodegenerative diseases; soft X-ray tomography (SXT); cancer; NDDs

Online: 5 December 2022 (02:27:26 CET)

Show abstract| Download PDF| Share

Working Paper ARTICLE

On the Combined Role of Strong and Electroweak Interactions in Understanding Nuclear Binding Energy Scheme

Satya Seshavatharam U.V., Lakshminarayana S.

Subject: Physical Sciences, Nuclear And High Energy Physics Keywords: 4G model of final unification; Four gravitational constants; Unified nuclear binding energy scheme; Free or unbound nucleons; Strong interaction; Electroweak interaction

Online: 25 December 2020 (17:29:44 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202301.0202.v1

Behavioural and Neurophysiological Assessment of Hearing Aid Benefits in an Adult Population with and without Hearing Loss

Shivali Appaiah-Konganda, Mridula Sharma, Ronny Ibrahim, Jessica J. M. Monaghan, John Newall, Joaquin Tomas Valderrama Valenzuela

Subject: Medicine And Pharmacology, Clinical Medicine Keywords: Alpha synchronisation; Working memory; Auditory processing; Modulation detection threshold

Online: 12 January 2023 (01:48:00 CET)

Show abstract| Download PDF| Share

Background: Despite hearing aids adequately compensate for hearing loss, a substantial proportion of the population leave their hearing difficulties untreated. Even though this is a well-known clinical issue, the optimal approach to address this issue during the hearing rehabilitation process is still unclear. Purpose: The present study aims to characterise behavioural and neurophysiological auditory and cognitive processing skills in experienced hearing aid users versus those with normal hearing, aimed at providing clinicians with the evidence required to adequately manage the expectations of their clients, thus indirectly reinforcing hearing-aid adoption within the adult population with hearing loss. Research design: Behavioural tests included auditory, cognitive, and speech-in-noise tasks; and neurophysiological testing included cortical auditory evoked potentials evoked by a /da/ stimulus presented at 65 dB SPL. The tests were selected based on previous literature supporting specific speech-understanding skills. Study sample: Ten participants (7 female, 21—68 years) with bilateral, mild-moderate to moderately-severe sensorineural hearing loss (HL), and 10 with clinically normal hearing (NH, 8 female, 19—62 years) participated in the study. Data collection and analysis: Behavioural data was analysed using multivariate analysis of variance (MANOVA) and neurophysiological analysis used measurements such as independent t-test, time-frequency analysis and inter-trial phase coherence. Results: The NH and HL groups presented similar scores in all the behavioural tasks. Time-frequency analysis revealed a statistically significantly reduction in alpha (8–12 Hz) synchronisation at the centro-frontal electrodes in the HL group – a brain activity pattern that has been associated with listening effort, inhibition and selective attention. Conclusions and significance: Results support the conclusion that hearing aids are effective in compensating for the audibility of their users, enabling them to perform at similar levels than their normal-hearing peers. However, the reduced alpha synchronisation observed in the HL population indicates that adequate audibility does not extend to improved neural responses. Future studies need to investigate the induced activity in speech understanding paradigms to explore the auditory processing differences at cortical level. The results are only from a small sample size but the findings have the potential to support clinicians in managing adequately the expectations of their clients in regards the benefits of hearing aid technologies.

Preprint ARTICLE | doi:10.20944/preprints202404.0837.v1

DITTO: An Explainable Machine-Learning Model for Transcript-Specific Variant Pathogenicity Prediction

Tarun Karthik Kumar Mamidi, Brandon M. Wilk, Manavalan Gajapathy, Elizabeth A. Worthey

Subject: Biology And Life Sciences, Life Sciences Keywords: rare disease; genomics; explainable; machine learning; pathogenic; variant consequence; classification; prioritization

Online: 12 April 2024 (09:59:40 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints202010.0017.v1

Transition from Electromechanical Dynamics to Quasi-Electromechanical Dynamics Caused by Participation of Full Converter-based Wind Power Generation

Jianqiang Luo, Siqi Bu

Subject: Engineering, Electrical And Electronic Engineering Keywords: Electromechanical dynamics; FCWG dynamics; strong interaction; electromechanical loop correlation ratio (ELCR); FCWG dynamic correlation ratio (FDCR); quasi- electromechanical loop correlation ratio (QELCR)

Online: 1 October 2020 (13:30:09 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202111.0460.v1

Low-Phosphate Meals Accompanied by a Minimum Dose of CaCO₃ Downregulates Pro-inflammation by Reducing CKD-MBD Indicators and Triggers by Decreasing Dietary Phosphate Intake

Barbara Ying-Jung Chen, Mei-Yi Wu, Mei-Yun Chin, Mai-Szu Wu, Jiun-Rong Chen

Subject: Medicine And Pharmacology, Dietetics And Nutrition Keywords: Maintenance hemodialysis (MHD) patient; Low-phosphate meal; CKD-MBD (chronic kidney disease-related mineral and bone disorder); Proinflammatory cytokine; TNF-α (tumor necrosis factor-alpha)

Online: 24 November 2021 (15:27:03 CET)

Show abstract| Download PDF| Share

High dietary phosphate intake and poor adherence to phosphate-binding-therapy elevate the risk of hyperphosphatemia in maintenance hemodialysis (HD; MHD) patients. Therefore, chronic kidney disease-related mineral and bone disorder (CKD-MBD) indicators increase; consequently, risks of CKD-MBDs and inflammation are elevated. This double-blind, randomized control trial intervention study was designed to investigate the possibility of reducing blood CKD-MBD indicators and modulating inflammatory indicators by consuming low-phosphate (LP) meals accompanied by a minimum dose of a calcium-based phosphate binder (CaCO3). MHD patients were recruited and randomly assigned to an LP meal group (LP group) or a control group. After initial data collection, blood collection, and dietary counseling, subjects were asked to consume a washout diet for 1 week. During the washout diet period, subjects consumed their usual diet but took 1 tablet of calcium carbonate (1CaCO3) as a phosphate binder with each meal. After the washout diet period, subjects in the LP group and control group respectively consumed LP meals and regular meals twice a day for 1 week. Meat in the LP meals was boiled before the regular cooking process, but meat in control meals was not. All meals were supplied by a central kitchen so that the contents of phosphate and other nutrients could be identified. In total, 40 MHD patients completed the study program. After 1 week of the dietary intervention, the blood Ca x P product and dietary phosphate had significantly decreased in the LP group compared to the control group (p<0.05). The LP group had significantly lower variations in dietary phosphate intake, blood calcium, Ca x P product, and tumor necrosis factor (TNF)-α than the control group by comparing differences between after the dietary intervention and the baseline (△after intervention - baseline, p<0.05). The increase in dietary phosphate intake (△3rd - 2nd dietary phosphate intake) augmented the increase in the TNF-α level by 6.24-fold (odds ratio [95% confidence interval]: 6.24 [1.12~34.92], p<0.05). These results highlighted the conclusion that LP meals accompanied by a minimum dose of CaCO3 downregulated pro-inflammation by reducing CKD-MBD indicators which was triggered by decreasing dietary phosphate intake.

Preprint ARTICLE | doi:10.20944/preprints202112.0520.v1

Strong Coupling Between Plasmonic Surface Lattice Resonance and Photonic Microcavity Modes

Yunjie Shi, Wei Liu, Shidi Liu, Tianyu Yang, Yuming Dong, Degui Sun, Guangyuan Li

Subject: Physical Sciences, Optics And Photonics Keywords: Strong coupling; plasmonic-photonic coupling system; surface lattice resonance; Fabry-Pérot resonance

Online: 31 December 2021 (12:42:38 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202009.0286.v1

Existence, Uniqueness and Input-To-State Stability of Ground-State Stationary Strong Solution of a Single-Species Model via Mountain Pass Lemma

Ruofeng Rao

Subject: Computer Science And Mathematics, Applied Mathematics Keywords: strong solution; regularity of weak Solutions; a single-species ecosystem; Lyapunov function; Mountain Pass Lemma; unique existence

Online: 13 September 2020 (12:26:12 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202303.0435.v1

Disease-Specific α-Synuclein Seeding and Structural Properties in Lewy Body Disease and Multiple System Atrophy are Preserved in Formaldehyde-Fixed Paraffin-Embedded Human Brain

Ain Kim, Ivan Martinez-Valbuena, Jun Li, Anthony E. Lang, Gabor Geza Kovacs

Subject: Medicine And Pharmacology, Medicine And Pharmacology Keywords: alpha-synuclein; protein extraction; FFPE; SAA; seeding behavior

Online: 27 March 2023 (03:23:29 CEST)

Show abstract| Download PDF| Supplementary Files| Share

Preprint ARTICLE | doi:10.20944/preprints202311.0115.v1

Exploring the Efficacy of AHA-BHA Infused Nanofiber Skin Masks as a Topical Treatment for Acne Vulgaris

Elçin Tören, Matěj Buzgo

Subject: Chemistry And Materials Science, Biomaterials Keywords: Acne vulgaris; hydroxy acids; alpha-hydroxy acids; beta-hydroxy acids; pullulan-collagen nanofibers; electrospinning; biocompatibility, topical treatment

Online: 2 November 2023 (04:09:05 CET)

Show abstract| Download PDF| Share

Acne vulgaris is a prevalent skin condition that affects people of all ages and can have significant physical and psychological impacts. Hydroxy acids, such as alpha-hydroxy acids (AHA) and beta-hydroxy acids (BHA), have demonstrated potential as effective ingredients for topical acne treatments due to their exfoliating and skin-rejuvenating properties. This study assessed the effectiveness of encapsulating AHA and BHA in pullulan-collagen nanofibers as a novel approach to acne treatment. The study involved preparing Pullulan and polyvinyl alcohol (PVA) solutions combined with sodium chloride (NaCl) to create a stable mixture. Collagen and Pullulan were then dissolved in deionized water and mixed to form a collagen-pullulan solution. Various weight ratios of Collagen to Pullulan were tested to optimize nanofiber formation. This research achieved electrospinning of nanofibers, confirmed by scanning electron microscopy (SEM) analysis, which revealed well-formed and continuous nanofiber structures in acidic solutions. Fourier transform infrared spectroscopy (FTIR) analysis provided insights into the chemical composition of the nanofibers, indicating the presence of ester, carboxylic acid, hydroxyl, and phenolic groups. Contact angle measurements demonstrated that the pullulan-collagen nanocomposite exhibited hydrophilic properties, albeit less hydrophilic than pure Collagen. Biocompatibility assays using mesenchymal stem cells (MSCs) and human skin fibroblasts (HSFs) revealed that the pullulan-collagen nanocomposite promoted higher cell viability compared to pure Collagen, suggesting its potential as a supportive matrix for cell growth and tissue regeneration. AHA-BHA-infused nanofiber skin masks hold promise as effective topical treatments for acne vulgaris. The successful encapsulation of hydroxy acids within pullulan-collagen nanofibers, in conjunction with their favourable chemical composition, hydrophilicity, and biocompatibility, positions them as promising candidates for delivering active ingredients and enhancing skin health. Further nanofiber formulation optimisation is necessary to exploit their therapeutic potential in skincare applications.

Preprint ARTICLE | doi:10.20944/preprints202401.1928.v3

Strengthening Pathogen and Antimicrobial Resistance Surveillance by Environmental Monitoring in Sub-Saharan Africa: A Stakeholder Survey

Ananda Tiwari, Taru Miller, Vito Baraka, Marc Tahita, Vivi Maketa, Berenger Kabore, Paul Kingpriest, Patrick Mitashi, Eric Lyimo, Hillary Sebukoto, Tarja Pitkänen

Subject: Environmental And Earth Sciences, Environmental Science Keywords: Wastewater; Waterborne pathogen; sub-Saharan African countries; environmental surveillance; prioritization

Online: 5 February 2024 (12:25:29 CET)

Show abstract| Download PDF| Share

Background: Waterborne diseases pose a significant global public health threat, compelling enhanced comprehensive surveillance. This study investigates the current infectious disease and antimicrobial resistance (AMR) surveillance systems, including wastewater and environmental surveillance (WES), in three sub-Saharan African countries: Tanzania, Burkina Faso, and the Democratic Republic of the Congo (DRC). The three countries have their specificities regarding wastewater networks and logistic systems. So, emphasizing the need to strengthen existing disease surveillance, the paper advocates for incorporating WES systems specifically designed for countries' context to monitor waterborne and re-emerging pathogens, as well as AMR.Methods: National workshops were conducted to assess the current clinical and environmental surveillance systems and identify priority pathogens for new environmental monitoring. Data were collected through surveys from experts in academia, research, policy, and healthcare. Results: Prioritized pathogens for WES include waterborne (poliovirus, Salmonella Typhi, Vibrio cholerae), respiratory (influenza A&B, SARS-CoV-2), other (Measles and Rubella, Mycobacterium tuberculosis). Recommended AMR pathogens include drug-resistant Mycobacterium tuberculosis, Salmonella spp., methicillin-resistant Staphylococcus aureus, and extended-spectrum beta-lactamase and carbapenemase-producing E. coli. Tanzania, Burkina Faso, and the DRC employ DHSI2-based centralized electronic systems for clinical data collection, complemented by Excel and paper-based registries. The WES approach is commonly employed for monitoring poliovirus and rarely for AMR and other pathogens. Discussion and conclusions: WES is a valuable tool for early detection of locally circulating human-derived pathogens, aiding in outbreak detection, data-driven epidemic response, and prevention. The availability of WES results underscores the importance of effective sanitation for safeguarding human, animal, and environmental health. WES is a pivotal tool for integrated risk management, preventing waterborne outbreaks, protecting drinking water sources, and ultimately gaining various UN Sustainable Development Goals. The study highlights the importance of customized WES systems in line with each country's context, emphasizing localized approaches for effective monitoring of waterborne pathogens and AMR.

Preprint COMMUNICATION | doi:10.20944/preprints202206.0117.v1

Formation of Stable Gold Nanoparticles from Cannabis Indica Leaves

Anjul Khadria, Subhankar Paul

Subject: Engineering, Other Keywords: Gold nanoparticles; nanomaterials; alpha-lactalbumin protein; Cannabis indica

Online: 8 June 2022 (05:59:13 CEST)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202304.0522.v1

A Tiny Viral Protein, SARS-CoV-2-ORF7b: Structural Features.

Giovanni Colonna

Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: ORF7b; SARS-CoV-2; COVID-19; 3D-structure; molecular dynamics; dipole vector; Electrostatic properties of alpha-helix.

Online: 18 April 2023 (11:14:01 CEST)

Show abstract| Download PDF| Supplementary Files| Share

ORF7b-2 is an accessory protein of the SARS-CoV-2 virus of only 43 amino acids. It has been implicated in various functional hypotheses, some of which predict its involvement as a trans-membrane protein. In this study, ORF7b-2 has often been compared to ORF7b-1 of the SARS virus to highlight differences and similarities with a protein that should have a similar biological role. Structural analysis of ORF7b-2 and its electrostatic characteristics show a polypeptide with both ends negatively charged and a diffuse negative charge over the entire structure. Therefore, its behavior in solution is like that of a weak negative polyelectrolyte, more precisely a polyanion with a net charge of – 4 at neutral pH. Its structure was modeled with two different modeling systems, one of which was ab initio. The two best models are similar, as confirmed by the Ramachandran plot, and show a central alpha-helical structure with two disordered and mobile ends. A normal mode analysis characterized the low-frequency dynamic aspects of the protein. The analysis of the structural shows a rigid central segment with mobile and fluctuating extremities, involved in a conformational equilibrium of the helix ↔ coil type. The calculation of the dipole moment shows its vector is not aligned with the main axis of the structure with an outward tilt of 24°. Molecular dynamics simulations were also conducted and the one in water is in good agreement with the previous results. While, the simulation performed by inserting a pre-oriented dimer (OMP) into a solvated lipid showed the low tendency of the protein to solvate in the apolar environment of the membrane. ORF7b-2 also shows a widespread distribution of negative surfaces that dynamically adjust to changes in structural organization. The BioGrid platform's [Biological General Repository for Interaction Datasets] through the BioGrid COVID-19 Coronavirus Curation Project shows a very large number of experimentally proven physical interactions unique to ORF7b-2, some of them with cytoplasmic proteins. These features of ORF7b-2, evaluated together, suggest a remarkable propensity of ORF7b-2 to interact with multiple molecular partners on both an electrostatic and hydrophobic basis. All this makes it unreasonable that the only biological function of this protein should be that exerted as an intramembrane protein.

Preprint ARTICLE | doi:10.20944/preprints202112.0177.v1

Chromatic Number and Neutrosophic Chromatic Number

Henry Garrett

Subject: Computer Science And Mathematics, Applied Mathematics Keywords: Neutrosophic Strong; Neutrosophic Graphs; Chromatic Number

Online: 10 December 2021 (13:08:38 CET)

Show abstract| Download PDF| Share

Preprint ARTICLE | doi:10.20944/preprints202403.0622.v1

Revealing Consequences of the Husking Process on Nutritional Profiles of Two Sorghum Races on the Male Sterility Line

Maha Khalfalla, László Zsombik, Zoltán Győri

Subject: Biology And Life Sciences, Agricultural Science And Agronomy Keywords: ; mineral contents, total protein, husking process, colour profile, S. bicolor, kafirin.

Online: 11 March 2024 (12:05:31 CET)

Show abstract| Download PDF| Share

Search Results

251 articles found