Fact Check: Assessing the Response of ChatGPT to Alzheimer's Disease Statements with Varying Degrees of Misinformation.

Background: There are many myths regarding Alzheimer's disease (AD) that have been circulated on the Internet, each exhibiting varying degrees of accuracy, inaccuracy, and misinformation. Large language models such as ChatGPT, may be a useful tool to help assess these myths for veracity and inaccuracy. However, they can induce misinformation as well. The objective of this study is to assess ChatGPT's ability to identify and address AD myths with reliable information. Methods: We conducted a cross-sectional study of clinicians' evaluation of ChatGPT (GPT 4.0)'s responses to 20 selected AD myths. We prompted ChatGPT to express its opinion on each myth and then requested it to rephrase its explanation using a simplified language that could be more readily understood by individuals with a middle school education. We implemented a survey using Redcap to determine the degree to which clinicians agreed with the accuracy of each ChatGPT's explanation and the degree to which the simplified rewriting was readable and retained the message of the original. We also collected their explanation on any disagreement with ChatGPT's responses. We used five Likert-type scale with a score ranging from -2 to 2 to quantify clinicians' agreement in each aspect of the evaluation. Results: The clinicians (n=11) were generally satisfied with ChatGPT's explanations, with a mean (SD) score of 1.0(±0.3) across the 20 myths. While ChatGPT correctly identified that all the 20 myths were inaccurate, some clinicians disagreed with its explanations on 7 of the myths.Overall, 9 of the 11 professionals either agreed or strongly agreed that ChatGPT has the potential to provide meaningful explanations of certain myths. Conclusions: The majority of surveyed healthcare professionals acknowledged the potential value of ChatGPT in mitigating AD misinformation. However, the need for more refined and detailed explanations of the disease's mechanisms and treatments was highlighted.

COVID-19, Framing and Naming a Pandemic: How What Is Not in a Disease Name May Be More Important than What Is.

While the disease name and acronym COVID-19, where 'CO' refers to 'corona', 'VI' to virus, 'D' to disease, and '19' the detection year, represents a rational, historically informed, and even culturally sensitive name choice by the World Health Organization, from the perspective of an ethnography of disease framing and naming, this study finds that it does not, however, readily communicate a public health message. This observation, based on linguistic and medical anthropological research and analyses, raises a critically important question: Can or should official disease names, beyond labeling medical conditions, also be designed to function as public health messages? As the ethnography of the term COVID-19 and its 'framing' demonstrates, using acronyms for disease names in public health can not only reduce their intelligibility but may also lower emerging public perceptions of risk, inadvertently, increasing the public's vulnerability. This study argues that the ongoing messaging and communication challenges surrounding the framing of COVID-19 and its variants represent an important opportunity for public health to engage social science research on language and risk communication to critically rethink disease naming and framing and how what they are called can prefigure and inform the public's uptake of science, understandings of risk, and the perceived importance of public health guidelines.

Cyanobacteria blooms: Maya peoples between the politics of risk and the threat of disaster.

In October of 2009 an outbreak of cyanobacteria in Lake Atitlán, Guatemala gained international attention and global news coverage with interests coming from environmentalists, microbiologists, and local health agencies. A significantly less well-known aspect of the crisis was the perceptions and predicaments of Maya (indigenous) peoples for whom the lake is the primary source of life and livelihood. This research examines the communication of the public health risk of cyanobacteria to Maya peoples. Using an "ethnography of risk communication" approach, this work traces the circulation of the science of cyanobacteria and the construction of risk from government and public health translations through media transmissions to local Maya interpretations. The findings demonstrate how government and institutional translations (and media transmissions) of the science of cyanobacteria not only unwittingly produced misunderstandings about the health dangers but indirectly associated blame for the outbreak with indigenous peoples, calling into question their way of life.

Maya mobile medicine in Guatemala: the "other" public health.

Maya mobile medical providers in highland Guatemala and the goods and services that they offer from "soapboxes" on street corners, local markets, and on buses exemplify an important yet underinvestigated domain of localized health care, one that I refer to as the "other" public health. This medical and linguistic examination of traveling medical salespeople calls for a reconsideration (on a global scale) of what has come to be understood as "public health," arguing that "othered," local forms of public health that are often overlooked by anthropologists as "nontraditional" and delegitimized by bio-medicine as nonscientific merit serious consideration and investigation. This ethnography of marginalized forms of public health offers global insights into emerging heterodoxical forms of public health care that contest bio-medical authority and challenge our preexisting definitions of what counts as "access," wellness seeking, and even health care itself.

Where there is no patient: an anthropological treatment of a biomedical category.

This work anthropologically applies the concept of 'personhood' to the Western biomedical patient role, and through cross-cultural comparisons with wellness-seeker roles (e.g. among the Maya of Guatemala and others) it seeks to discern the implications for global healthcare of assuming the universality of the "patient" role. Here, particular ethnographic attention is given to the presumption of the "patient" role in places and situations where, because of cultural and linguistic variation in local wellness-seeker roles and practices, there may be no "patient." It is hoped that establishing the biomedical patient role (with the clinical expectations, communicative and comportment practices that prefigure it) as acquired rather than intuitive, will help redirect cultural competence to the acquisition of patienthood, broadening it from an endless accrual of cultural inventories by physicians. Also it aims to shift existing biomedical associations of cultural variations in wellness-seeking away from a priori assessments of clinical defiance towards deeper understandings of the kinds of cultural differences that may make the difference treatment outcomes.

NMR structure of human erythropoietin and a comparison with its receptor bound conformation.

The solution structure of human erythropoietin (EPO) has been determined by nuclear magnetic resonance spectroscopy and the overall topology of the protein is revealed as a novel combination of features taken from both the long-chain and short-chain families of hematopoietic growth factors. Using the structure and data from mutagenesis studies we have elucidated the key physiochemical properties defining each of the two receptor binding sites on the EPO protein. A comparison of the NMR structure of the free EPO ligand to the receptor bound form, determined by X-ray crystallography, reveals conformational changes that may accompany receptor binding.

Discrimination of DNA binding sites by mutant p53 proteins.

Critical determinants of DNA recognition by p53 have been identified by a molecular genetic approach. The wild-type human p53 fragment containing amino acids 71 to 330 (p53(71-330)) was used for in vitro DNA binding assays, and full-length human p53 was used for transactivation assays with Saccharomyces cerevisiae. First, we defined the DNA binding specificity of the wild-type p53 fragment by using systematically altered forms of a known consensus DNA site. This refinement indicates that p53 binds with high affinity to two repeats of PuGPuCA.TGPyCPy, a further refinement of an earlier defined consensus half site PuPuPuC(A/T).(T/A) GPyPyPy. These results were further confirmed by transactivation assays of yeast by using full-length human p53 and systematically altered DNA sites. Dimers of the pentamer AGGCA oriented either head-to-head or tail-to-tail bound efficiently, but transactivation was facilitated only through head-to-head dimers. To determine the origins of specificity in DNA binding by p53, we identified mutations that lead to altered specificities of DNA binding. Single-amino-acid substitutions were made at several positions within the DNA binding domain of p53, and this set of p53 point mutants were tested with DNA site variants for DNA binding. DNA binding analyses showed that the mutants Lys-120 to Asn, Cys-277 to Gln or Arg, and Arg-283 to Gln bind to sites with noncanonical base pair changes at positions 2, 3, and 1 in the pentamer (PuGPuCA), respectively. Thus, we implicate these residues in amino acid-base pair contacts. Interestingly, mutant Cys-277 to Gln bound a consensus site as two and four monomers, as opposed to the wild-type p53 fragment, which invariably binds this site as four monomers.

Sequestration of the membrane-targeting myristoyl group of recoverin in the calcium-free state.

Recoverin, a retinal calcium-binding protein of relative molecular mass (M(r)) 23K, participates in the recovery phase of visual excitation and in adaptation to background light. The Ca(2+)-bound form of recoverin prolongs the photoresponse, probably by blocking phosphorylation of photoexcited rhodopsin. Retinal recoverin contains a covalently attached myristoyl group or related acyl group at its amino terminus and two Ca(2+)-binding sites. Ca2+ binding to myristoylated, but not unmyristoylated, recoverin induces its translocation to bilayer membranes, indicating that the myristoyl group is essential to the read-out of calcium signals (calcium-myristoyl switch). Here we present the solution structure of Ca(2+)-free, myristoylated recombinant recoverin obtained by heteronuclear multidimensional NMR spectroscopy. The myristoyl group is sequestered in a deep hydrophobic pocket formed by many aromatic and other hydrophobic residues from five flanking helices.

Solution structure of a cellulose-binding domain from Cellulomonas fimi by nuclear magnetic resonance spectroscopy.

Multidimensional, multinuclear nuclear magnetic resonance spectroscopy combined with dynamical simulated annealing has been used to determine the structure of a 110 amino acid cellulose-binding domain (CBD) from Cex, a beta-1,4-glycanase from the bacterium Cellulomonas fimi (CBDcex). An experimental data set comprising 1795 interproton NOE-derived restraints, 50 phi, 34 chi 1, and 106 hydrogen bond restraints was used to calculate 20 final structures. The calculated structures have an average root-mean-square (rms) deviation about the mean structure of 0.41 A for backbone atoms and 0.67 A for all heavy atoms when fitted over the secondary structural elements. Chromatography, ultracentrifugation, and 15N NMR relaxation experiments demonstrate that CBDcex is a dimer in solution. While attempts to measure NOEs across the dimer interface were unsuccessful, a computational strategy was employed to generate dimer structures consistent with the derived data set. The results from the dimer calculations indicate that, while the monomer topologies produced in the context of the dimer can be variable, the relative positioning of secondary structural elements and side chains present in the monomer are restored upon dimer formation. CBDcex forms an extensive beta-sheet structure with a beta-barrel fold. Titration with cellohexaose, [beta-D-glucopyranosyl-(1,4)]5-D-glucose, establishes that Trp 54 and 72 participate in cellulose binding. Analysis of the structure shows that these residues are adjacent in space and exposed to solvent. Together with other proximate hydrophilic residues, these residues form a carbohydrate-binding cleft, which appears to be a feature common to all CBDs of the same family.

Solution structure of the epithelial cadherin domain responsible for selective cell adhesion.

Cadherins are calcium-dependent cell adhesion molecules containing extracellular repeats of approximately 110 amino acids. The three-dimensional structure of the amino-terminal repeat of mouse epithelial cadherin was determined by multidimensional heteronuclear magnetic resonance spectroscopy. The calcium ion was bound by a short alpha helix and by loops at one end of the seven-stranded beta-barrel structure. An exposed concave face is in a position to provide homophilic binding specificity and was also sensitive to calcium ligation. Unexpected structural similarities with the immunoglobulin fold suggest an evolutionary relation between calcium-dependent and calcium-independent cell adhesion molecules.

Solution structure of the tetrameric minimum transforming domain of p53.

We report the solution structure of the minimum transforming domain (residues 303-366) of human p53 (p53tet) determined by multidimensional NMR spectroscopy. This domain contains a number of important functions associated with p53 activity including transformation, oligomerization, nuclear localization and a phosphorylation site for p34/cdc2 kinase. p53tet forms a symmetric dimer of dimers that is significantly different from a recent structure reported for a shorter construct of this domain. Phosphorylation of Ser 315 has only minor structural consequences, as this region of the protein is unstructured. Modelling based on the p53tet structure suggests possible modes of interaction between adjacent domains in full-length p53 as well as modes of interaction with DNA.

Structural similarity of a developmentally regulated bacterial spore coat protein to beta gamma-crystallins of the vertebrate eye lens.

The solution structure of Ca(2+)-loaded protein S (M(r) 18,792) from the Gram-negative soil bacterium Myxococcus xanthus has been determined by multidimensional heteronuclear NMR spectroscopy. Protein S consists of four internally homologous motifs, arranged to produce two domains with a pseudo-twofold symmetry axis, overall resembling a triangular prism. Each domain consists of two topologically inequivalent "Greek keys": the second and fourth motifs form standard Greek keys, whereas the first and third motifs each contain a regular alpha-helix in addition to the usual four beta-strands. The structure of protein S is similar to those of the vertebrate eye lens beta gamma-crystallins, which are thought to be evolutionarily related to protein S. Both protein S and the beta gamma-crystallins function by forming stable multimolecular assemblies. However, protein S possesses distinctive motif organization and domain packing, indicating a different mode of oligomerization and a divergent evolutionary pathway from the beta gamma-crystallins.

High-resolution solution structure of reduced parsley plastocyanin.

A high-resolution three-dimensional solution structure of parsley plastocyanin has been determined using 1H-NMR-derived data. An ensemble of 30 conformers has been calculated, exhibiting an atomic root mean square distribution about the mean coordinate positions of 0.37 +/- 0.03 A for backbone atoms and 0.75 +/- 0.04 A for all heavy atoms. (These values exclude residues 8-10 which are disordered.) The global fold of parsley plastocyanin is closely similar to those of other plastocyanins which have been structurally characterized by X-ray diffraction and NMR methods. However, deletion of residues at positions 57 and 58 of the consensus plastocyanin sequence causes elimination of a turn found in most higher plant plastocyanins. This turn is located in an acidic patch binding site, which consists of two clusters of acidic residues at positions 42-45 and 59-61. These residues surround the side chain of Tyr 83, which has been shown to be involved in binding of and electron transfer from cytochrome f, one of plastocyanin's physiological partners. The acidic recognition site is further disrupted in parsley plastocyanin by nonconservative substitution of two charged residues at positions 59 and 60. The NMR-derived structures show that E53, E85, and E95 compensate for these substitutions and give parsley plastocyanin an acidic recognition site of similar extent to that of other higher plant plastocyanins.(ABSTRACT TRUNCATED AT 250 WORDS)

Unusual helix-containing greek keys in development-specific Ca(2+)-binding protein S. 1H, 15N, and 13C assignments and secondary structure determined with the use of multidimensional double and triple resonance heteronuclear NMR spectroscopy.

Multidimensional heteronuclear NMR spectroscopy has been used to determine almost complete backbone and side-chain 1H, 15N, and 13C resonance assignments of calcium loaded Myxococcus xanthus protein S (173 residues). Of the range of constant-time triple resonance experiments recorded, HNCACB and CBCA(CO)NH, which correlate C alpha and C beta with backbone amide resonances of the same and the succeeding residue respectively, proved particularly useful in resolving assignment ambiguities created by the 4-fold internal homology of the protein S amino acid sequence. Extensive side-chain 1H and 13C assignments have been obtained by analysis of HCCH-TOCSY and 15N-edited TOCSY-HMQC spectra. A combination of NOE, backbone amide proton exchange, 3JNH alpha coupling constant, and chemical shift data has been used to show that each of the protein S repeat units consists of four beta-strands in a Greek key arrangement. Two of the Greek keys contain a regular alpha-helix between the third and fourth strands, resulting in an unusual and possibly unique variation on this common folding motif. Despite similarity between two nine-residue stretches in the first and third domains of protein S and one of the Ca(2+)-binding sequences in bovine brain calmodulin [Inouye, S., Franceschini, T., & Inouye, M. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 6829-6833], the protein S topology in these regions is incompatible with an EF-hand calmodulin-type Ca(2+)-binding site.

NMR-derived three-dimensional solution structure of protein S complexed with calcium.

BACKGROUND: Protein S is a developmentally-regulated Ca(2+)-binding protein of the soil bacterium Myxococcus xanthus. It functions by forming protective, multilayer spore surface assemblies which may additionally act as a cell-cell adhesive. Protein S is evolutionarily related to vertebrate lens beta gamma-crystallins. RESULTS: The three-dimensional solution structure of Ca(2+)-loaded protein S has been determined using multi-dimensional heteronuclear NMR spectroscopy. (Sixty structures were calculated, from which thirty were selected with a root mean square difference from the mean of 0.38 A for backbone atoms and 1.22 A for all non-hydrogen atoms.) The structure was analyzed and compared in detail with X-ray crystallographic structures of beta gamma-crystallins. The two internally homologous domains of protein S were compared, and hydrophobic cores, domain interfaces, surface ion pairing, amino-aromatic interactions and potential modes of multimerization are discussed. CONCLUSIONS: Structural features of protein S described here help to explain its overall thermostability, as well as the higher stability and Ca2+ affinity of the amino-terminal domain relative to the carboxy-terminal domain. Two potential modes of multimerization are proposed involving cross-linking of protein S molecules through surface Ca(2+)-binding sites and formation of the intramolecular protein S or gamma B-crystallin interdomain interface in an intermolecular content. This structural analysis may also have implications for Ca(2+)-dependent cell-cell interactions mediated by the vertebrate cadherins and Dictyostelium discoideum protein gp24.

Solution structure of a pair of fibronectin type 1 modules with fibrin binding activity.

The tertiary structure of the fourth and fifth type 1 module pair from the N terminus of human fibronectin, has been determined by two-dimensional homonuclear 1H nuclear magnetic resonance (NMR) spectroscopy. Comparison of each module fold with those of two other type 1 modules shows that the type 1 "consensus" structure is conserved in the pair. The modules connect end-to-end to form an elongated structure with a limited clockwise twist around the long axis, from N to C terminus. The short five residue linker sequence forms a tight loop and the relative orientation of the two modules is maintained by fixed and intimate hydrophobic contacts, dominated by a non-conserved tryptophan residue from the fourth type 1 module. The protein binds specifically to fibrin in an ELISA and surface accessible residues that may be involved in this and other protein interactions can be identified. The structure provides an insight into how chains of type 1 modules may link up in intact fibronectin.

A calmodulin-target peptide hybrid molecule with unique calcium-binding properties.

This paper describes the production and properties of a hybrid protein comprising the full length of the Xenopus laevis calmodulin (CaM) sequence, followed, through a glycylglycine linker, by the 26-residue CaM-binding region of myosin light-chain kinase (M13). This hybrid molecule appears to have high thermal stability (Tm > 75 degrees C in the presence of Ca2+) as well as unusual Ca(2+)-binding properties: (i) a wide-range biphasic Ca(2+)-binding response (extending over pCa 4.8-7.4) and (ii) a high apparent binding constant (pCa50% = 6.3, a 10-fold increase from that of wild-type CaM). NMR and CD data indicate that the CaM-M13 hybrid molecule exists in equilibrium in an approximate 1:1 ratio between two major conformations, one of which is similar to the compact globular structure of the CaM-M13 complex [M.Ikura, G.M. Clore, A.M. Gronenborn, G. Zhu, C.B. Klee and A. Bax (1992) Science, 256, 632-638] and the other to the dumb-bell-like structure of the wild type CaM [Y.S. Babu, C.E. Bugg and W.J. Cook (1988) J. Mol. Biol., 204, 191-204]. The biphasic Ca(2+)-binding curve can be interpreted using a linear combination of two Hill binding curves with significantly different dissociation constants (2 x 10(-9) M and 8 x 10(-8) M), which can be attributed to the two conformations in equilibrium. The present study has opened an avenue to engineer proteins with higher Ca(2+)-binding affinities using the known CaM structures as a template.

The three-dimensional structure of the tenth type III module of fibronectin: an insight into RGD-mediated interactions.

The solution structure of the tenth type III module of fibronectin has been determined using nuclear magnetic resonance techniques. The molecule has a fold similar to that of immunoglobulin domains, with seven beta strands forming two antiparallel beta sheets, which pack against each other. Both beta sheets contribute conserved hydrophobic residues to a compact core. The topology is more similar to that of domain 2 of CD4, PapD, and the extracellular domain of the human growth hormone receptor than to that of immunoglobulin C domains. The module contains an Arg-Gly-Asp sequence known to be involved in cell adhesion. This tripeptide is solvent exposed and lies on a conformationally mobile loop between strands F and G, consistent with its cell adhesion function.

Human epidermal growth factor. High resolution solution structure and comparison with human transforming growth factor alpha.

The solution structure of the 53 amino acid peptide hormone, human epidermal growth factor (hEGF), has been determined to high resolution from nuclear magnetic resonance (n.m.r.) data. A large number of internuclear distance and dihedral restraints was obtained, including data from uniformly 15N-labelled hEGF. Dynamical simulated annealing methods using the program XPLOR were used for structure calculation. An improved protocol was developed combining efficient conformational searching at a reduced computational cost. The general fold of the calculated structures compared well with that of a derivative of the carboxy-terminally truncated hEGF determined previously. A group of 44 structures were calculated with no violations greater than 0.3 A and 3 degrees for distance and dihedral restraints, respectively. The average pairwise root mean square (r.m.s.) deviation of all backbone atoms for these structures was 2.25 A for all 53 residues, 0.92 A for the bulk of the protein, and 0.23 A for the functionally important carboxy-terminal domain. Two new helical segments containing highly conserved amino acids have been identified; one between cysteines 6 and 14 and a second at the end of the carboxy-terminal domain. New insight into the molecular architecture of the site of putative receptor binding was provided by comparing the structure of hEGF with its biologically equipotent analogue, human transforming growth factor alpha. This comparison revealed a close structural relationship between the two growth factors and provides an improved understanding of the structure/function relationships in EGF.