Display omitted
•Cryptic and allosteric binding sites are increasingly important for drug discovery.•FTMove is a program that identifies important binding sites from multiple conformations of a ...protein.•User input is as simple as a PDB code and chain ID, making the program easily accessible.•FTMove maps each protein conformation and runs a clustering algorithm to determine the consensus binding sites.•The structures are clustered on the basis of their binding properties.
Protein mapping distributes many copies of different molecular probes on the surface of a target protein in order to determine binding hot spots, regions that are highly preferable for ligand binding. While mapping of X-ray structures by the FTMap server is inherently static, this limitation can be overcome by the simultaneous analysis of multiple structures of the protein. FTMove is an automated web server that implements this approach. From the input of a target protein, by PDB code, the server identifies all structures of the protein available in the PDB, runs mapping on them, and combines the results to form binding hot spots and binding sites. The user may also upload their own protein structures, bypassing the PDB search for similar structures. Output of the server consists of the consensus binding sites and the individual mapping results for each structure - including the number of probes located in each binding site, for each structure. This level of detail allows the users to investigate how the strength of a binding site relates to the protein conformation, other binding sites, and the presence of ligands or mutations. In addition, the structures are clustered on the basis of their binding properties. The use of FTMove is demonstrated by application to 22 proteins with known allosteric binding sites; the orthosteric and allosteric binding sites were identified in all but one case, and the sites were typically ranked among the top five. The FTMove server is publicly available at https://ftmove.bu.edu.
The field of palaeomicrobiology is dramatically expanding thanks to recent advances in high-throughput biomolecular sequencing, which allows unprecedented access to the evolutionary history and ...ecology of human-associated and environmental microbes. Recently, human dental calculus has been shown to be an abundant, nearly ubiquitous, and long-term reservoir of the ancient oral microbiome, preserving not only microbial and host biomolecules but also dietary and environmental debris. Modern investigations of native human microbiota have demonstrated that the human microbiome plays a central role in health and chronic disease, raising questions about changes in microbial ecology, diversity and function through time. This paper explores the current state of ancient oral microbiome research and discusses successful applications, methodological challenges and future possibilities in elucidating the intimate evolutionary relationship between humans and their microbes.
Paleoproteomics Warinner, Christina; Korzow Richter, Kristine; Collins, Matthew J.
Chemical reviews,
08/2022, Letnik:
122, Številka:
16
Journal Article
Recenzirano
Odprti dostop
Paleoproteomics, the study of ancient proteins, is a rapidly growing field at the intersection of molecular biology, paleontology, archaeology, paleoecology, and history. Paleoproteomics research ...leverages the longevity and diversity of proteins to explore fundamental questions about the past. While its origins predate the characterization of DNA, it was only with the advent of soft ionization mass spectrometry that the study of ancient proteins became truly feasible. Technological gains over the past 20 years have allowed increasing opportunities to better understand preservation, degradation, and recovery of the rich bioarchive of ancient proteins found in the archaeological and paleontological records. Growing from a handful of studies in the 1990s on individual highly abundant ancient proteins, paleoproteomics today is an expanding field with diverse applications ranging from the taxonomic identification of highly fragmented bones and shells and the phylogenetic resolution of extinct species to the exploration of past cuisines from dental calculus and pottery food crusts and the characterization of past diseases. More broadly, these studies have opened new doors in understanding past human–animal interactions, the reconstruction of past environments and environmental changes, the expansion of the hominin fossil record through large scale screening of nondiagnostic bone fragments, and the phylogenetic resolution of the vertebrate fossil record. Even with these advances, much of the ancient proteomic record still remains unexplored. Here we provide an overview of the history of the field, a summary of the major methods and applications currently in use, and a critical evaluation of current challenges. We conclude by looking to the future, for which innovative solutions and emerging technology will play an important role in enabling us to access the still unexplored “dark” proteome, allowing for a fuller understanding of the role ancient proteins can play in the interpretation of the past.
Defamatory publications may carry any number of related or distinct imputations. Complexities arise where a plaintiff selects one or more imputations for complaint, but ignores other imputations ...carried by the same publication. In England and Wales, the so-called Polly Peck principle permits defendants to plead and justify an imputation other than one complained of by the plaintiff but bearing a common sting with such an imputation. The Polly Peck principle has not been good law in Australia for more than 20 years. The statutory defence of contextual truth in Australia’s uniform defamation laws, however, permits a defendant to plead and justify imputations that are ‘in addition to’ those complained of by the plaintiff and affords a complete defence where, having regard to the substantial truth of those contextual imputations, the imputations complained of by the plaintiff do not further harm the reputation of the plaintiff. As enacted, the defence was infected with a serious drafting error. This article looks at the implications of the reformulation of the contextual truth defence effected by the recent amendments to Australia’s uniform defamation laws. It posits that those implications are considerably broader than have been recognised to date. It argues that the reformulated defence not only corrects the drafting error in the original defence of contextual truth but also resurrects the Polly Peck principle in Australia and substantially neuters 20 years of confused jurisprudence concerning the extent to which a defendant is or should be constrained by the imputations pleaded by the plaintiff.
Tissue-thin parchment made it possible to produce the first pocket Bibles: Thousands were made in the 13th century. The source of this parchment, often called “uterine vellum,” has been a ...long-standing controversy in codicology. Use of the Latin termabortivumin many sources has led some scholars to suggest that the skin of fetal calves or sheep was used. Others have argued that it would not be possible to sustain herds if so many pocket Bibles were produced from fetal skins, arguing instead for unexpected alternatives, such as rabbit. Here, we report a simple and objective technique using standard conservation treatments to identify the animal origin of parchment. The noninvasive method is a variant on zooarchaeology by mass spectrometry (ZooMS) peptide mass fingerprinting but extracts protein from the parchment surface by using an electrostatic charge generated by gentle rubbing of a PVC eraser on the membrane surface. Using this method, we analyzed 72 pocket Bibles originating in France, England, and Italy and 293 additional parchment samples that bracket this period. We found no evidence for the use of unexpected animals; however, we did identify the use of more than one mammal species in a single manuscript, consistent with the local availability of hides. These results suggest that ultrafine vellum does not necessarily derive from the use of abortive or newborn animals with ultrathin hides, but could equally well reflect a production process that allowed the skins of maturing animals of several species to be rendered into vellum of equal quality and fineness.
A quantum computer attains computational advantage when outperforming the best classical computers running the best-known algorithms on well-defined tasks. No photonic machine offering ...programmability over all its quantum gates has demonstrated quantum computational advantage: previous machines
were largely restricted to static gate sequences. Earlier photonic demonstrations were also vulnerable to spoofing
, in which classical heuristics produce samples, without direct simulation, lying closer to the ideal distribution than do samples from the quantum hardware. Here we report quantum computational advantage using Borealis, a photonic processor offering dynamic programmability on all gates implemented. We carry out Gaussian boson sampling
(GBS) on 216 squeezed modes entangled with three-dimensional connectivity
, using a time-multiplexed and photon-number-resolving architecture. On average, it would take more than 9,000 years for the best available algorithms and supercomputers to produce, using exact methods, a single sample from the programmed distribution, whereas Borealis requires only 36 μs. This runtime advantage is over 50 million times as extreme as that reported from earlier photonic machines. Ours constitutes a very large GBS experiment, registering events with up to 219 photons and a mean photon number of 125. This work is a critical milestone on the path to a practical quantum computer, validating key technological features of photonics as a platform for this goal.
One-dimensional models with topological band structures represent a simple and versatile platform to demonstrate novel topological concepts. Here we experimentally study topologically protected ...states in silicon at the interface between two dimer chains with different Zak phases. Furthermore, we propose and demonstrate that, in a system where topological and trivial defect modes coexist, we can probe them independently. Tuning the configuration of the interface, we observe the transition between a single topological defect and a compound trivial defect state. These results provide a new paradigm for topologically protected waveguiding in a complementary metal-oxide-semiconductor compatible platform and highlight the novel concept of isolating topological and trivial defect modes in the same system that can have important implications in topological physics.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of ...government public health policies depends on accurate data on SARS-CoV-2 immunity at a population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a noninvasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at a population scale. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology that comprised 12 CoV antigens, mostly derived from SARS-CoV-2 nucleocapsid (N) and spike (S). Saliva and sera collected from confirmed coronavirus disease 2019 (COVID-19) cases and from the pre-COVID-19 era were tested for IgG, IgA, and IgM to the antigen panel. Matched saliva and serum IgG responses (
= 28) were significantly correlated. The salivary anti-N IgG response resulted in the highest sensitivity (100%), exhibiting a positive response in 24/24 reverse transcription-PCR (RT-PCR)-confirmed COVID-19 cases sampled at >14 days post-symptom onset (DPSO), whereas the salivary anti-receptor binding domain (RBD) IgG response yielded 100% specificity. Temporal kinetics of IgG in saliva were consistent with those observed in blood and indicated that most individuals seroconvert at around 10 DPSO. Algorithms employing a combination of the IgG responses to N and S antigens result in high diagnostic accuracy (100%) by as early as 10 DPSO. These results support the use of saliva-based antibody testing as a noninvasive and scalable alternative to blood-based antibody testing.
Cross-reactive antibodies elicited by dengue virus (DENV) infection might affect Zika virus infection and confound serologic tests. Recent data demonstrate neutralization of Zika virus by monoclonal ...antibodies or human serum collected early after DENV infection. Whether this finding is true in late DENV convalescence (>6 months after infection) is unknown. We studied late convalescent serum samples from persons with prior DENV or Zika virus exposure. Despite extensive cross-reactivity in IgG binding, Zika virus neutralization was not observed among primary DENV infections. We observed low-frequency (23%) Zika virus cross-neutralization in repeat DENV infections. DENV-immune persons who had Zika virus as a secondary infection had distinct populations of antibodies that neutralized DENVs and Zika virus, as shown by DENV-reactive antibody depletion experiments. These data suggest that most DENV infections do not induce durable, high-level Zika virus cross-neutralizing antibodies. Zika virus-specific antibody populations develop after Zika virus infection irrespective of prior DENV immunity.
PDF
