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Article: Materialism.

Melnyk, Andrew

Wiley interdisciplinary reviews. Cognitive science

2012 Volume 3, Issue 3, Page(s) 281–292

Abstract: Materialism is nearly universally assumed by cognitive scientists. Intuitively, materialism says that a person's mental states are nothing over and above his or her material states, while dualism denies this. Philosophers have introduced concepts (e.g., ... ...

Abstract	Materialism is nearly universally assumed by cognitive scientists. Intuitively, materialism says that a person's mental states are nothing over and above his or her material states, while dualism denies this. Philosophers have introduced concepts (e.g., realization and supervenience) to assist in formulating the theses of materialism and dualism with more precision, and distinguished among importantly different versions of each view (e.g., eliminative materialism, substance dualism, and emergentism). They have also clarified the logic of arguments that use empirical findings to support materialism. Finally, they have devised various objections to materialism, objections that therefore serve also as arguments for dualism. These objections typically center around two features of mental states that materialism has had trouble in accommodating. The first feature is intentionality, the property of representing, or being about, objects, properties, and states of affairs external to the mental states. The second feature is phenomenal consciousness, the property possessed by many mental states of there being something it is like for the subject of the mental state to be in that mental state. WIREs Cogn Sci 2012, 3:281-292. doi: 10.1002/wcs.1174 For further resources related to this article, please visit the WIREs website.
Language	English
Publishing date	2012-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2553336-8
ISSN	1939-5086 ; 1939-5078
ISSN (online)	1939-5086
ISSN	1939-5078
DOI	10.1002/wcs.1174
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Article ; Online: The C. difficile toxin B membrane translocation machinery is an evolutionarily conserved protein delivery apparatus.

Orrell, Kathleen E / Mansfield, Michael J / Doxey, Andrew C / Melnyk, Roman A

Nature communications

2020 Volume 11, Issue 1, Page(s) 432

Abstract: Large Clostridial Toxins (LCTs) are a family of six homologous protein toxins that are implicated in severe disease. LCTs infiltrate host cells using a translocation domain (LCT-T) that contains both cell-surface receptor binding sites and a membrane ... ...

Abstract	Large Clostridial Toxins (LCTs) are a family of six homologous protein toxins that are implicated in severe disease. LCTs infiltrate host cells using a translocation domain (LCT-T) that contains both cell-surface receptor binding sites and a membrane translocation apparatus. Despite much effort, LCT translocation remains poorly understood. Here we report the identification of 1104 LCT-T homologs, with 769 proteins from bacteria outside of clostridia. Sequences are widely distributed in pathogenic and host-associated species, in a variety of contexts and architectures. Consistent with these homologs being functional toxins, we show that a distant LCT-T homolog from Serratia marcescens acts as a pH-dependent translocase to deliver its effector into host cells. Based on evolutionary footprinting of LCT-T homologs, we further define an evolutionarily conserved translocase region that we show is an autonomous translocase capable of delivering heterologous cargo into host cells. Our work uncovers a broad class of translocating toxins and provides insights into LCT translocation.
MeSH term(s)	Amino Acid Sequence ; Animals ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Bacterial Toxins/chemistry ; Bacterial Toxins/genetics ; Bacterial Toxins/metabolism ; Biological Evolution ; Chlorocebus aethiops ; Circular Dichroism ; Clostridioides difficile/metabolism ; Clostridioides difficile/pathogenicity ; Conserved Sequence ; Evolution, Molecular ; HCT116 Cells ; Host-Pathogen Interactions ; Humans ; Hydrogen-Ion Concentration ; Protein Domains ; Protein Transport ; Sequence Homology, Amino Acid ; Serratia marcescens/metabolism ; Serratia marcescens/pathogenicity ; Vero Cells
Chemical Substances	Bacterial Proteins ; Bacterial Toxins ; toxB protein, Clostridium difficile
Language	English
Publishing date	2020-01-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-14306-z
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Article ; Online: Structures of distant diphtheria toxin homologs reveal functional determinants of an evolutionarily conserved toxin scaffold.

Sugiman-Marangos, Seiji N / Gill, Shivneet K / Mansfield, Michael J / Orrell, Kathleen E / Doxey, Andrew C / Melnyk, Roman A

Communications biology

2022 Volume 5, Issue 1, Page(s) 375

Abstract: Diphtheria toxin (DT) is the archetype for bacterial exotoxins implicated in human diseases and has played a central role in defining the field of toxinology since its discovery in 1888. Despite being one of the most extensively characterized bacterial ... ...

Abstract	Diphtheria toxin (DT) is the archetype for bacterial exotoxins implicated in human diseases and has played a central role in defining the field of toxinology since its discovery in 1888. Despite being one of the most extensively characterized bacterial toxins, the origins and evolutionary adaptation of DT to human hosts remain unknown. Here, we determined the first high-resolution structures of DT homologs outside of the Corynebacterium genus. DT homologs from Streptomyces albireticuli (17% identity to DT) and Seinonella peptonophila (20% identity to DT), despite showing no toxicity toward human cells, display significant structural similarities to DT sharing both the overall Y-shaped architecture of DT as well as the individual folds of each domain. Through a systematic investigation of individual domains, we show that the functional determinants of host range extend beyond an inability to bind cellular receptors; major differences in pH-induced pore-formation and cytosolic release further dictate the delivery of toxic catalytic moieties into cells, thus providing multiple mechanisms for a conserved structural fold to adapt to different hosts. Our work provides structural insights into the expanding DT family of toxins, and highlights key transitions required for host adaptation.
MeSH term(s)	Bacterial Toxins ; Diphtheria Toxin/chemistry ; Diphtheria Toxin/genetics ; Diphtheria Toxin/toxicity ; Humans
Chemical Substances	Bacterial Toxins ; Diphtheria Toxin
Language	English
Publishing date	2022-04-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-022-03333-9
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Article ; Online: Three-dimensional printed hydrogel model vs cadaver: comparing inflatable penile prosthesis training and evaluation.

Saba, Patrick / Cook, Andrew / Melnyk, Rachel / Schuler, Nathan / Holler, Tyler / Witthaus, Michael / Ralph, David / Collins, Justin / Bettocchi, Carlo / Van Renterghem, Koenraad / Ghazi, Ahmed

The journal of sexual medicine

2023 Volume 20, Issue 8, Page(s) 1126–1132

Abstract: Background: Penile prosthesis implantation offers a durable, safe, and effective treatment option for male erectile dysfunction; however, many urologists feel apprehensive and uncomfortable placing penile prostheses due to limited training, low surgical ...

Abstract	Background: Penile prosthesis implantation offers a durable, safe, and effective treatment option for male erectile dysfunction; however, many urologists feel apprehensive and uncomfortable placing penile prostheses due to limited training, low surgical experience, and intra- and postoperative complication management. Aim: To compare a previously validated hydrogel inflatable penile prosthesis (IPP) training model with cadaver simulations across 4 main categories: anatomic replication and realism, procedural replication and realism, educational effectiveness, and efficacy and safety. Methods: An overall 88 participants (15 attendings, 18 fellows, and 55 residents) performed guided IPP placements on a cadaver and a hydrogel model. Based on a 5-point Likert scale, postsurveys were used to assess the participants' opinions regarding anatomic replication and realism, procedural replication and realism, educational effectiveness, and safety between the hydrogel model and cadavers. Outcomes: A direct head-to-head scenario was created, allowing participants to fully utilize the hydrogel model and cadaver, which ensured the most accurate comparison possible. Results: A total of 84% agreed that the hydrogel model replicates the relevant human cadaveric anatomy for the procedure, whereas 69% agreed that the hydrogel tissue resembles the appearance of cadaveric tissue. Regarding the pubic bone, outer skin, corporal bodies, dartos layer, and scrotum, 79%, 74%, 82%, 46%, and 30% respectively agreed that the hydrogel tissue resembled the texture/behavior of cadavers. Furthermore, 66% of participants agreed that the hydrogel model replicates all the procedural steps. Specifically, participants agreed that the model replicates the skin incision/dartos dissection (74%), placement of stay suture and corporotomy (92%), corporal dilation (81%), measurement of prosthetic size (98%), reservoir placement (43%), IPP placement (91%), scrotal pump placement (48%), and skin closure (51%). Finally, 86%, 93%, and 78% agreed that the hydrogel model is useful for improving technical skills, as a teaching/practicing tool, and as an evaluation tool, respectively. To conclude, 81% of participants stated that they would include the hydrogel model platform in their current training. Clinical implications: By replicating the IPP procedure, the hydrogel model offers an additional high-fidelity training opportunity for urologists, allowing them to improve their skills and confidence in placing penile prostheses, with the goal of improving patient surgical outcomes. Strengths and limitations: The hydrogel training model allows users to perform the entire IPP placement procedure with high anatomic realism and educational effectiveness, maintaining many of the high-fidelity benefits seen in cadavers while improving safety and accessibility. Conclusion: Ultimately, this high-fidelity nonbiohazardous training model can be used to supplement and bolster current IPP training curriculums.
MeSH term(s)	Male ; Humans ; Penile Prosthesis/adverse effects ; Hydrogels ; Penile Implantation/methods ; Erectile Dysfunction/surgery ; Erectile Dysfunction/etiology ; Cadaver
Chemical Substances	Hydrogels
Language	English
Publishing date	2023-08-02
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2251959-2
ISSN	1743-6109 ; 1743-6095
ISSN (online)	1743-6109
ISSN	1743-6095
DOI	10.1093/jsxmed/qdad071
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Article ; Online: Using earth mover's distance for viral outbreak investigations.

Melnyk, Andrew / Knyazev, Sergey / Vannberg, Fredrik / Bunimovich, Leonid / Skums, Pavel / Zelikovsky, Alex

BMC genomics

2020 Volume 21, Issue Suppl 5, Page(s) 582

Abstract: Background: RNA viruses mutate at extremely high rates, forming an intra-host viral population of closely related variants, which allows them to evade the host's immune system and makes them particularly dangerous. Viral outbreaks pose a significant ... ...

Abstract	Background: RNA viruses mutate at extremely high rates, forming an intra-host viral population of closely related variants, which allows them to evade the host's immune system and makes them particularly dangerous. Viral outbreaks pose a significant threat for public health, and, in order to deal with it, it is critical to infer transmission clusters, i.e., decide whether two viral samples belong to the same outbreak. Next-generation sequencing (NGS) can significantly help in tackling outbreak-related problems. While NGS data is first obtained as short reads, existing methods rely on assembled sequences. This requires reconstruction of the entire viral population, which is complicated, error-prone and time-consuming. Results: The experimental validation using sequencing data from HCV outbreaks shows that the proposed algorithm can successfully identify genetic relatedness between viral populations, infer transmission direction, transmission clusters and outbreak sources, as well as decide whether the source is present in the sequenced outbreak sample and identify it. Conclusions: Introduced algorithm allows to cluster genetically related samples, infer transmission directions and predict sources of outbreaks. Validation on experimental data demonstrated that algorithm is able to reconstruct various transmission characteristics. Advantage of the method is the ability to bypass cumbersome read assembly, thus eliminating the chance to introduce new errors, and saving processing time by allowing to use raw NGS reads.
MeSH term(s)	Algorithms ; Disease Outbreaks ; Hepacivirus/genetics ; High-Throughput Nucleotide Sequencing ; RNA Viruses
Language	English
Publishing date	2020-12-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2041499-7
ISSN	1471-2164 ; 1471-2164
ISSN (online)	1471-2164
ISSN	1471-2164
DOI	10.1186/s12864-020-06982-4
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Article ; Online: Structures of distant diphtheria toxin homologs reveal functional determinants of an evolutionarily conserved toxin scaffold

Seiji N. Sugiman-Marangos / Shivneet K. Gill / Michael J. Mansfield / Kathleen E. Orrell / Andrew C. Doxey / Roman A. Melnyk

Communications Biology, Vol 5, Iss 1, Pp 1-

2022 Volume 12

Abstract: Toxic proteins are responsible for the disease symptoms accompanying bacterial infections. Sugiman-Marangos et al. report crystal structures of two diphtheria toxin homologs, therefore providing structural insights into this family of toxins and the ... ...

Abstract	Toxic proteins are responsible for the disease symptoms accompanying bacterial infections. Sugiman-Marangos et al. report crystal structures of two diphtheria toxin homologs, therefore providing structural insights into this family of toxins and the evolutionary adaptation of these toxins to human hosts.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: From Alpha to Zeta: Identifying Variants and Subtypes of SARS-CoV-2 Via Clustering.

Melnyk, Andrew / Mohebbi, Fatemeh / Knyazev, Sergey / Sahoo, Bikram / Hosseini, Roya / Skums, Pavel / Zelikovsky, Alex / Patterson, Murray

Journal of computational biology : a journal of computational molecular cell biology

2021 Volume 28, Issue 11, Page(s) 1113–1129

Abstract: The availability of millions of SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) sequences in public databases such as GISAID (Global Initiative on Sharing All Influenza Data) and EMBL-EBI (European Molecular Biology Laboratory-European ... ...

Abstract	The availability of millions of SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) sequences in public databases such as GISAID (Global Initiative on Sharing All Influenza Data) and EMBL-EBI (European Molecular Biology Laboratory-European Bioinformatics Institute) (the United Kingdom) allows a detailed study of the evolution, genomic diversity, and dynamics of a virus such as never before. Here, we identify novel variants and subtypes of SARS-CoV-2 by clustering sequences in adapting methods originally designed for haplotyping intrahost viral populations. We asses our results using clustering entropy-the first time it has been used in this context. Our clustering approach reaches lower entropies compared with other methods, and we are able to boost this even further through gap filling and Monte Carlo-based entropy minimization. Moreover, our method clearly identifies the well-known Alpha variant in the U.K. and GISAID data sets, and is also able to detect the much less represented (<1% of the sequences) Beta (South Africa), Epsilon (California), and Gamma and Zeta (Brazil) variants in the GISAID data set. Finally, we show that each variant identified has high selective fitness, based on the growth rate of its cluster over time. This demonstrates that our clustering approach is a viable alternative for detecting even rare subtypes in very large data sets.
MeSH term(s)	Brazil ; Cluster Analysis ; Computational Biology/methods ; Databases, Genetic ; Entropy ; Humans ; Monte Carlo Method ; South Africa ; United Kingdom ; United States
Language	English
Publishing date	2021-10-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2030900-4
ISSN	1557-8666 ; 1066-5277
ISSN (online)	1557-8666
ISSN	1066-5277
DOI	10.1089/cmb.2021.0302
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Article ; Online: The C. difficile toxin B membrane translocation machinery is an evolutionarily conserved protein delivery apparatus

Kathleen E. Orrell / Michael J. Mansfield / Andrew C. Doxey / Roman A. Melnyk

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 11

Abstract: Large Clostridial toxins infiltrate host cells using a translocation domain (LCT-T). Here, using a genomics-driven approach and functional assays, the authors uncover the presence of distant LCT-T homologs in bacteria outside clostridia and provide ... ...

Abstract	Large Clostridial toxins infiltrate host cells using a translocation domain (LCT-T). Here, using a genomics-driven approach and functional assays, the authors uncover the presence of distant LCT-T homologs in bacteria outside clostridia and provide evidence for a toxic effector function in the gammaproteobacterium Serratia marcescens.
Keywords	Science ; Q
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Role of Race and Gender in Nutrition Habits and Self-Efficacy: Results from the Young Adult Weight Loss Study.

Stephens, Janna D / Althouse, Andrew / Tan, Alai / Melnyk, Bernadette Mazurek

Journal of obesity

2017 Volume 2017, Page(s) 5980698

Abstract: Overweight and obesity are a massive public health problem and young adults are at high risk for gaining weight once they enter a college. This study sought to examine gender and race as they relate to nutrition habits and self-efficacy in a population ... ...

Abstract	Overweight and obesity are a massive public health problem and young adults are at high risk for gaining weight once they enter a college. This study sought to examine gender and race as they relate to nutrition habits and self-efficacy in a population of diverse young adults from the Young Adult Weight Loss Study. Participants (
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article
ZDB-ID	2573566-4
ISSN	2090-0716 ; 2090-0708
ISSN (online)	2090-0716
ISSN	2090-0708
DOI	10.1155/2017/5980698
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Article ; Online: Correction to: Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder.

Zimmerman, Andrew W / Singh, Kanwaljit / Connors, Susan L / Liu, Hua / Panjwani, Anita A / Lee, Li-Ching / Diggins, Eileen / Foley, Ann / Melnyk, Stepan / Singh, Indrapal N / Jill James, S / Frye, Richard E / Fahey, Jed W

Molecular autism

2021 Volume 12, Issue 1, Page(s) 44

Language	English
Publishing date	2021-06-16
Publishing country	England
Document type	Published Erratum
ZDB-ID	2540930-X
ISSN	2040-2392 ; 2040-2392
ISSN (online)	2040-2392
ISSN	2040-2392
DOI	10.1186/s13229-021-00451-9
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