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The Last Interglacial (LIG; ca. 125,000 y ago) resulted from rapid global warming and reached global mean temperatures exceeding those of today. The LIG thus offers the opportunity to study how life may respond to future global warming. Using global occurrence databases and applying sampling-standardization, we compared reef coral diversity and distributions between the LIG and modern. Latitudinal diversity patterns are characterized by a tropical plateau today but were characterized by a pronounced equatorial trough during the LIG. This trough is governed by substantial range shifts away from the equator. Range shifts affected both leading and trailing edges of species range limits and were much more pronounced in the Northern Hemisphere than south of the equator. We argue that interglacial warming was responsible for the loss of equatorial diversity. Hemispheric differences in insolation during the LIG may explain the asymmetrical response. The equatorial retractions are surprisingly strong given that only small temperature changes have been reported in the LIG tropics. Our results suggest that the poleward range expansions of reef corals occurring with intensified global warming today may soon be followed by equatorial range retractions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants are a continuous threat to human life. An urgent need remains for simple and fast tests that reliably detect active infections with SARS-CoV-2 and its variants in the early stage of infection. Here we introduce a simple and rapid activity-based diagnostic (ABDx) test that identifies SARS-CoV-2 infections by measuring the activity of a viral enzyme, Papain-Like protease (PLpro). The test system consists of a peptide that fluoresces when cleaved by SARS PLpro that is active in crude, unprocessed lysates from human tongue scrapes and saliva. Test results are obtained in 30 minutes or less using widely available fluorescence plate readers, or a battery-operated portable instrument for on-site testing. Proof-of-concept was obtained in a study on clinical specimens collected from patients with COVID-19 like symptoms who tested positive (n = 10) or negative (n = 10) with LIAT RT-PCR using nasal mid turbinate swabs. When saliva from these patients was tested with in-house endpoint RT-PCR, 17 were positive and only 5 specimens were negative, of which 2 became positive when tested 5 days later. PLpro activity correlated in 17 of these cases (3 out of 3 negatives and 14 out of 16 positives, with one invalid specimen). Despite the small number of samples, the agreement was significant (p value = 0.01). Two false negatives were detected, one from a sample with a late Ct value of 35 in diagnostic RT-PCR, indicating that an active infection was no longer present. The PLpro assay is easily scalable and expected to detect all viable SARS-CoV-2 variants, making it attractive as a screening and surveillance tool. Additionally, we show feasibility of the platform as a new homogeneous phenotypic assay for rapid screening of SARS-CoV-2 antiviral drugs and neutralizing antibodies.

DNA replication produces tangled, or catenated, chromatids, that must be decatenated prior to mitosis or catastrophic genomic damage will occur. Topoisomerase IIalpha (Topo IIalpha) is the primary decatenating enzyme. Cells monitor catenation status and activate decatenation checkpoints when decatenation is incomplete, which occurs when Topo IIalpha is inhibited by chemotherapy agents such as the anthracyclines and epididophyllotoxins. We recently demonstrated that the DNA repair component Metnase (also called SETMAR) enhances Topo IIalpha-mediated decatenation, and hypothesized that Metnase could mediate resistance to Topo IIalpha inhibitors. Here we show that Metnase interacts with Topo IIalpha in breast cancer cells, and that reducing Metnase expression significantly increases metaphase decatenation checkpoint arrest. Repression of Metnase sensitizes breast cancer cells to Topo IIalpha inhibitors, and directly blocks the inhibitory effect of the anthracycline adriamycin on Topo IIalpha-mediated decatenation in vitro. Thus, Metnase may mediate resistance to Topo IIalpha inhibitors, and could be a biomarker for clinical sensitivity to anthracyclines. Metnase could also become an important target for combination chemotherapy with current Topo IIalpha inhibitors, specifically in anthracycline-resistant breast cancer.

Specific protein interactions are responsible for most biological functions. Distinguishing Functionally Linked Interfaces of Proteins (FLIPs), from Functionally uncorrelated Contacts (FunCs), is therefore important to characterizing these interactions. To achieve this goal, we have created a database of protein structures called FLIPdb, containing proteins belonging to various functional sub-categories. Here, we use geometric features coupled with Kortemme and Baker's computational alanine scanning method to calculate the energetic sensitivity of each amino acid at the interface to substitution, identify hotspots, and identify other factors that may contribute towards an interface being FLIP or FunC. Using Principal Component Analysis and K-means clustering on a training set of 160 interfaces, we could distinguish FLIPs from FunCs with an accuracy of 76%. When these methods were applied to two test sets of 18 and 170 interfaces, we achieved similar accuracies of 78% and 80%. We have identified that FLIP interfaces have a stronger central organizing tendency than FunCs, due, we suggest, to greater specificity. We also observe that certain functional sub-categories, such as enzymes, antibody-heavy-light, antibody-antigen, and enzyme-inhibitors form distinct sub-clusters. The antibody-antigen and enzyme-inhibitors interfaces have patterns of physical characteristics similar to those of FunCs, which is in agreement with the fact that the selection pressures of these interfaces is differently evolutionarily driven. As such, our ECR model also successfully describes the impact of evolution and natural selection on protein-protein interfaces. Finally, we indicate how our ECR method may be of use in reducing the false positive rate of docking calculations.

In their pre-scientific world, miracles were taken for granted. [...]this morning, don’t think about the miracle, think about the message. The glory of God is seen in the life and death of Jesus, especially on the cross. Because God is love, he suffers with us and because of us, and in Jesus offers us life.

In the past decade, the field of coral reef restoration has experienced a proliferation of data detailing the source, genetics, and performance of coral strains used in research and restoration. Resource managers track the multitude of permits, species, restoration locations, and performance across multiple stakeholders while researchers generate large data sets and data pipelines detailing the genetic, genomic, and phenotypic variants of corals. Restoration practitioners, in turn, maintain records on fragment collection, genet performance, outplanting location and survivorship. While each data set is important in its own right, collectively they can provide deeper insights into coral biology and better guide coral restoration endeavors – unfortunately, current data sets are siloed with limited ability to cross-mine information for deeper insights and hypothesis testing. Herein we present the Coral Sample Registry (CSR), an online resource that establishes the first step in integrating diverse coral restoration data sets. Developed in collaboration with academia, management agencies, and restoration practitioners in the South Florida area, the CSR centralizes information on sample collection events by issuing a unique accession number to each entry. Accession numbers can then be incorporated into existing and future data structures. Each accession number is unique and corresponds to a specific collection event of coral tissue, whether for research, archiving, or restoration purposes. As such the accession number can serve as the key to unlock the diversity of information related to that sample’s provenance and characteristics across any and all data structures that include the accession number field. The CSR is open-source and freely available to users, designed to be suitable for all coral species in all geographic regions. Our goal is that this resource will be adopted by researchers, restoration practitioners, and managers to efficiently track coral samples through all data structures and thus enable the unlocking of a broader array of insights.

Specific protein interactions are responsible for most biological functions. Distinguishing Functionally Linked Interfaces of Proteins (FLIPs), from Functionally uncorrelated Contacts (FunCs), is therefore important to characterizing these interactions. To achieve this goal, we have created a database of protein structures called FLIPdb, containing proteins belonging to various functional sub-categories. Here, we use geometric features coupled with Kortemme and Baker's computational alanine scanning method to calculate the energetic sensitivity of each amino acid at the interface to substitution, identify hotspots, and identify other factors that may contribute towards an interface being FLIP or FunC. Using Principal Component Analysis and K-means clustering on a training set of 160 interfaces, we could distinguish FLIPs from FunCs with an accuracy of 76%. When these methods were applied to two test sets of 18 and 170 interfaces, we achieved similar accuracies of 78% and 80%. We have identified that FLIP interfaces have a stronger central organizing tendency than FunCs, due, we suggest, to greater specificity. We also observe that certain functional sub-categories, such as enzymes, antibody-heavy-light, antibody-antigen, and enzyme-inhibitors form distinct sub-clusters. The antibody-antigen and enzyme-inhibitors interfaces have patterns of physical characteristics similar to those of FunCs, which is in agreement with the fact that the selection pressures of these interfaces is differently evolutionarily driven. As such, our ECR model also successfully describes the impact of evolution and natural selection on protein-protein interfaces. Finally, we indicate how our ECR method may be of use in reducing the false positive rate of docking calculations.

To determine if testing environment affects Balance Error Scoring System (BESS) scores in healthy collegiate baseball players. Experimental, randomized, repeated-measures design with a sample of convenience. Uncontrolled sideline and controlled locker room baseball environments. A total of 21 healthy collegiate baseball players (age = 20.1 +/- 1.4 years, height = 185.1 +/- 6.8 cm, mass = 86.3 +/- 9.5 kg) with no history of head injury within the last 12 months, no lower extremity injuries reported within the past 2 months that caused them to miss 1 or more days of practice or game time, and no history of otitis media, Parkinson disease, or Meniere disease. Participants performed the BESS test in 2 environments, controlled locker room and uncontrolled sideline, in 2 testing sessions 1 week apart during the baseball preseason. The BESS scores were evaluated for each of the 6 conditions and total score across the testing sessions. Separate, paired-samples t tests with Bonferroni adjustment (P < .008) were used to examine differences between testing environments for each BESS subcategory and total score. Cohen d tests were calculated to evaluate effect sizes and relative change. Significant group mean differences were found between testing environments for single-leg foam stance (P = .001), with higher scores reported for the uncontrolled sideline environment (7.33 +/- 2.11 errors) compared with the controlled clinical environment (5.19 +/- 2.16 errors). Medium to large effect sizes (0.53 to 1.03) were also found for single-leg foam, tandem foam, and total BESS scores, with relative increases (worse scores) of 30% to 44% in the sideline environment compared with the clinical environment. The BESS performance was impaired when participants were tested in a sideline environment compared with a clinical environment. Baseline testing for postural control using the BESS should be conducted in the setting or environment in which testing after injury will most likely be conducted.

ATCC 49444, originally designated as Staphylococcus aureus, has been cited as a component strain in the CAMP test for identification of Listeria monocytogenes. A polyphasic study, in which molecular data were combined with cytochemical properties and physiological characteristics, identified this isolate as Staphylococcus pseudintermedius. The nucleotide sequences of the 16S rRNA and sodA genes from ATCC 49444 were determined and found to be identical to those of other S. pseudintermedius strains. Ribotyping analysis of ATCC 49444 indicated a low (0.2) similarity index with S. aureus and Staphylococcus intermedius strains but a similarity index of more than 0.66 with S. pseudintermedius isolates. A functional comparison of ATCC 49444 with S. aureus ATCC 25923 utilizing the CAMP test demonstrated equivalent hemolytic enhancement with L. monocytogenes isolates. While this study demonstrates that ATCC 49444 is a valid component strain for the CAMP test, it is proposed that ATCC 49444 be reclassified as S. pseudintermedius and that users worldwide be alerted to this reclassification and name change.

A sequence determinant of reduction potentials is reported for bacterial [4Fe-4S]-type ferredoxins. The residue that is four residues C-terminal to the fourth ligand of either cluster is generally an alanine or a cysteine. In five experimental ferredoxin structures, the cysteine has the same structural orientation relative to the nearest cluster, which is stabilized by the SH···S bond. Although such bonds are generally considered weak, indications that Fe-S redox site sulfurs are better hydrogen-bond acceptors than most sulfurs include the numerous amide NH···S bonds noted by Adman and our quantum mechanical calculations. Furthermore, electrostatic potential calculations of 11 experimental ferredoxin structures indicate that the extra cysteine decreases the reduction potential relative to an alanine by ∼60 mV, in agreement with experimental mutational studies. Moreover, the decrease in potential is due to a shift in the polar backbone stabilized by the SH···S bond rather than to the slightly polar cysteinyl side chain. Thus, these cysteines can “tune” the reduction potential, which could optimize electron flow in an electron transport chain. More generally, hydrogen bonds involving sulfur can be important in protein structure/function, and mutations causing polar backbone shifts can alter electrostatics and thus affect redox properties or even enzymatic activity of a protein.