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Background: Osteochondritis dissecans (OCD) of the capitellum is a well-described condition that most commonly affects adolescent throwing athletes and gymnasts. There is no gold standard rehabilitation protocol or timing for return to sport (RTS) after surgical management of OCD of the capitellum. Hypothesis/Purpose: The purpose of the study was to identify in the existing literature any criteria used for RTS following surgical treatment of OCD of the capitellum. The hypothesis was that surgeons would utilize length of time rather than functional criteria or performance benchmarks for RTS. Methods: Level 1 to 4 studies evaluating athletes who underwent surgery for OCD of the capitellum with a minimum follow-up of 1-year were included. Studies not describing RTS criteria, including less than 1-year follow-up, non-operative management only, and revision procedures were excluded. Each study was analyzed for RTS criteria, RTS rate, RTS timeline, sport played, level of competition, graft source (if utilized), and postoperative rehabilitation parameters. Assessment of bias and methodological quality was performed using the Coleman methodology score and RTS value assessment. Results: All studies reported a rehabilitation protocol with immobilization followed by bracing with progressive range of motion. RTS rate was 80.9% (233/288). The majority of studies reported using time-based criteria for RTS (11/15). The most commonly reported timeline was 6 months (range: 3-12 months). Conclusion: The overall RTS rate after surgical treatment of capitellar OCD is high with no consensus on RTS criteria. The two most consistent RTS criteria reported in the literature are return of elbow range of motion and healing demonstrated on postoperative imaging. There is a wide range of time to RTS in the literature, which may be sport dependent. Further research is needed to develop functional and performance-based metrics to better standardize RTS criteria and rehabilitation protocols.

Volcanic activity has been shown to affect Earth's climate in a myriad of ways. One such example is that eruptions proximate to surface ice will promote ice melting. In turn, the crustal unloading associated with melting an ice sheet affects the internal dynamics of the underlying magma plumbing system. Geochronologic data from the Andes over the last two glacial cycles suggest that glaciation and volcanism may interact via a positive feedback loop. At present, accurate sea-level predictions hinge on our ability to forecast the stability of the West Antarctic Ice Sheet, and thus require consideration of two-way subglacial volcano-deglaciation processes. The West Antarctic Ice Sheet is particularly vulnerable to collapse, yet its position atop an active volcanic rift is seldom considered. Ice unloading deepens the zone of melting and alters the crustal stress field, impacting conditions for dike initiation, propagation, and arrest. However, the consequences for internal magma chamber dynamics and long-term eruption behavior remain elusive. Given that unloading-triggered volcanism in West Antarctica may contribute to the uncertainty of ice loss projections, we adapt a previously published thermomechanical magma chamber model and simulate a shrinking ice load through a prescribed lithostatic pressure decrease. We investigate the impacts of varying unloading scenarios on magma volatile partitioning and eruptive trajectory. Considering the removal of km-thick ice sheets, we demonstrate that the rate of unloading influences the cumulative mass erupted and consequently the heat released into the ice. These findings provide fundamental insights into the complex volcano-ice interactions in West Antarctica and other subglacial volcanic settings., Competing Interests: The authors declare no conflicts of interest relevant to this study., (© 2024 The Author(s). Geochemistry, Geophysics, Geosystems published by Wiley Periodicals LLC on behalf of American Geophysical Union.)

The timing, tempo, and causative mechanisms of Ocean Anoxic Event 1a (OAE1a), one of several such abrupt perturbations of the Mesozoic global carbon cycle, remain uncertain. Mudstones interbedded with tuffs in Hokkaido, Japan preserve carbon and osmium isotope shifts recording OAE1a. U-Pb zircon ages of tuffs constrain the OAE1a onset to 119.55 +0.072/-0.079 million years ago (Ma) and its duration to 1116 +87/-93 thousand years (kyr). Isotopic excursions of osmium followed by carbon that mark the rapid onset of OAE1a each lasted ~115 kyr. Critically, the occurrence of index fossil Leupoldina cabri in the Hokkaido OAE1a section, which also caps and thus postdate Ontong Java Plateau (OJP) basalts, has a U-Pb zircon age of ~118.7 to 118.4 Ma. Therefore, OJP volcanism remains a probable source of unradiogenic osmium and light carbon and a causative mechanism of OAE1a.

Rhyolitic melt that fuels explosive eruptions often originates in the upper crust via extraction from crystal-rich sources, implying an evolutionary link between volcanism and residual plutonism. However, the time scales over which these systems evolve are mainly understood through erupted deposits, limiting confirmation of this connection. Exhumed plutons that preserve a record of high-silica melt segregation provide a critical subvolcanic perspective on rhyolite generation, permitting comparison between time scales of long-term assembly and transient melt extraction events. Here, U-Pb zircon petrochronology and 40 Ar/ 39 Ar thermochronology constrain silicic melt segregation and residual cumulate formation in a ~7 to 6 Ma, shallow (3 to 7 km depth) Andean pluton. Thermo-petrological simulations linked to a zircon saturation model map spatiotemporal melt flux distributions. Our findings suggest that ~50 km 3 of rhyolitic melt was extracted in ~130 ka, transient pluton assembly that indicates the thermal viability of advanced magma differentiation in the upper crust., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Reversal of Earth's magnetic field polarity every 10 5 to 10 6 years is among the most far-reaching, yet enigmatic, geophysical phenomena. The short duration of reversals make precise temporal records of past magnetic field behavior paramount to understanding the processes that produce them. We correlate new 40 Ar/ 39 Ar dates from transitionally magnetized lava flows to astronomically dated sediment and ice records to map the evolution of Earth's last reversal. The final 180° polarity reversal at ~773 ka culminates a complex process beginning at ~795 ka with weakening of the field, succeeded by increased field intensity manifested in sediments and ice, and then by an excursion and weakening of intensity at ~784 ka that heralds a >10 ka period wherein sediments record highly variable directions. The 22 ka evolution of this reversal suggested by our findings is mirrored by a numerical geodynamo simulation that may capture much of the naturally observed reversal process.

Large rhyolitic volcanoes pose a hazard, yet the processes and signals foretelling an eruption are obscure. Satellite geodesy has revealed surface inflation signaling unrest within magma reservoirs underlying a few rhyolitic volcanoes. Although seismic, electrical, and potential field methods may illuminate the current configuration and state of these reservoirs, they cannot fully address the processes by which they grow and evolve on geologic time scales. We combine measurement of a deformed paleoshore surface, isotopic dating of volcanism and surface exposure, and modeling to determine the rate of growth of a rhyolite-producing magma reservoir. The numerical approach builds on a magma intrusion model developed to explain the current, decade-long, surface inflation at >20 cm/year. Assuming that the observed 62-m uplift reflects several non-eruptive intrusions of magma, each similar to the unrest over the past decade, we find that ~13 km 3 of magma recharged the reservoir at a depth of ~7 km during the Holocene, accompanied by the eruption of ~9 km 3 of rhyolite. The long-term rate of magma input is consistent with reservoir freezing and pluton formation. Yet, the unique set of observations considered here implies that large reservoirs can be incubated and grow at shallow depth via episodic high-flux magma injections. These replenishment episodes likely drive rapid inflation, destabilize cooling systems, propel rhyolitic eruptions, and thus should be carefully monitored.

Accurate and precise ages of large silicic eruptions are critical to calibrating the geologic timescale and gauging the tempo of changes in climate, biologic evolution, and magmatic processes throughout Earth history. The conventional approach to dating these eruptive products using the 40 Ar/ 39 Ar method is to fuse dozens of individual feldspar crystals. However, dispersion of fusion dates is common and interpretation is complicated by increasingly precise data obtained via multicollector mass spectrometry. Incremental heating of 49 individual Bishop Tuff (BT) sanidine crystals produces 40 Ar/ 39 Ar dates with reduced dispersion, yet we find a 16-ky range of plateau dates that is not attributable to excess Ar. We interpret this dispersion to reflect cooling of the magma reservoir margins below ∼475 °C, accumulation of radiogenic Ar, and rapid preeruption remobilization. Accordingly, these data elucidate the recycling of subsolidus material into voluminous rhyolite magma reservoirs and the effect of preeruptive magmatic processes on the 40 Ar/ 39 Ar system. The youngest sanidine dates, likely the most representative of the BT eruption age, yield a weighted mean of 764.8 ± 0.3/0.6 ka (2σ analytical/full uncertainty) indicating eruption only ∼7 ky following the Matuyama-Brunhes magnetic polarity reversal. Single-crystal incremental heating provides leverage with which to interpret complex populations of 40 Ar/ 39 Ar sanidine and U-Pb zircon dates and a substantially improved capability to resolve the timing and causal relationship of events in the geologic record., Competing Interests: The authors declare no conflict of interest.

Aims: Growth differentiation factor 11 and/or its homologue growth differentiation factor 8 (GDF11/8) reverses age-related cardiac hypertrophy and vascular ageing in mice. We investigated whether GDF11/8 associates with cardiovascular outcomes, left ventricular hypertrophy (LVH), or age in humans., Methods and Results: We measured plasma GDF11/8 levels in 928 participants with stable ischaemic heart disease in the Heart and Soul study. We adjudicated heart failure hospitalization, stroke, myocardial infarction, death, and their composite endpoint. Left ventricular hypertrophy was evaluated by echocardiography. We used multivariable Cox proportional hazards models to compare rates of cardiovascular events and death across GDF11/8 quartiles and logistic regression models to evaluate the association between GDF11/8 and LVH. Four hundred and fifty participants (48.5%) experienced a cardiovascular event or death during 8.9 years of follow-up. The adjusted risk of the composite endpoint was lower in the highest compared with the lowest GDF11/8 quartile [hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.33-0.60; P < 0.001]. We replicated this relationship of GDF11/8 to adverse events in 971 participants in the HUNT3 cohort (adjusted HR, 0.34; 95% CI, 0.23-0.51; P < 0.001). Left ventricular hypertrophy was present in 368 participants (39.7%) at baseline. Participants in the highest quartile of GDF11/8 were less likely to have LVH than those in the lowest quartile (adjusted OR, 0.55; 95% CI, 0.35-0.86; P = 0.009). GDF11/8 levels were lower in older individuals (P < 0.001)., Conclusion: In patients with stable ischaemic heart disease, higher GDF11/8 levels are associated with lower risk of cardiovascular events and death. Our findings suggest that GDF11/8 has similar cardioprotective properties in humans to those demonstrated in mice., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

The most common form of heart failure occurs with normal systolic function and often involves cardiac hypertrophy in the elderly. To clarify the biological mechanisms that drive cardiac hypertrophy in aging, we tested the influence of circulating factors using heterochronic parabiosis, a surgical technique in which joining of animals of different ages leads to a shared circulation. After 4 weeks of exposure to the circulation of young mice, cardiac hypertrophy in old mice dramatically regressed, accompanied by reduced cardiomyocyte size and molecular remodeling. Reversal of age-related hypertrophy was not attributable to hemodynamic or behavioral effects of parabiosis, implicating a blood-borne factor. Using modified aptamer-based proteomics, we identified the TGF-β superfamily member GDF11 as a circulating factor in young mice that declines with age. Treatment of old mice to restore GDF11 to youthful levels recapitulated the effects of parabiosis and reversed age-related hypertrophy, revealing a therapeutic opportunity for cardiac aging., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We present evidence that the source of Earth's axial dipole field is largely independent from the sources responsible for the rest of the geomagnetic field, the so-called nonaxial dipole (NAD) field. Support for this claim comes from correlations between the structure of the historic field and the behavior of the paleomagnetic field recorded in precisely dated lavas at those times when the axial dipole was especially weak or nearly absent. It is argued that a "stratification" of magnetic sources exists in the fluid core such that the axial dipole is the only observed field component that is nearly immune from the influence exerted by the lowermost mantle. It follows that subsequent work on spherical harmonic-based field descriptions may now incorporate an understanding of a dichotomy of spatial-temporal dynamo processes.

Whether cooling occurred in the Southern Hemisphere during the Younger Dryas (YD) is key to understanding mechanisms of millennial climate change. Although Southern Hemisphere records do not reveal a distinct climate reversal during the late glacial period, many mountain glaciers readvanced. We show that the Puerto Bandera moraine (50 degrees S), which records a readvance of the Southern Patagonian Icefield (SPI), formed at, or shortly after, the end of the YD. The exposure age (10.8 +/- 0.5 thousand years ago) is contemporaneous with the highest shoreline of Lago Cardiel (49 degrees S), which records peak precipitation east of the Andes since 13 thousand years ago. Absent similar moraines west of the Andes, these data indicate an SPI response to increased amounts of easterly-sourced precipitation-reflecting changes in the Southern Westerly circulation-rather than regional cooling.

The origins of South America's exceptional plant diversity are poorly known from the fossil record. We report on unbiased quantitative collections of fossil floras from Laguna del Hunco (LH) and Río Pichileufú (RP) in Patagonia, Argentina. These sites represent a frost-free humid biome in South American middle latitudes of the globally warm Eocene. At LH, from 4,303 identified specimens, we recognize 186 species of plant organs and 152 species of leaves. Adjusted for sample size, the LH flora is more diverse than comparable Eocene floras known from other continents. The RP flora shares several taxa with LH and appears to be as rich, although sampling is preliminary. The two floras were previously considered coeval. However, (40)Ar/(39)Ar dating of three ash-fall tuff beds in close stratigraphic association with the RP flora indicates an age of 47.46+/-0.05 Ma, 4.5 million years younger than LH, for which one tuff is reanalyzed here as 51.91+/-0.22 Ma. Thus, diverse floral associations in Patagonia evolved by the Eocene, possibly in response to global warming, and were persistent and areally extensive. This suggests extraordinary richness at low latitudes via the latitudinal diversity gradient, corroborated by published palynological data from the Eocene of Colombia.

Reversals of the Earth's magnetic field reflect changes in the geodynamo--flow within the outer core--that generates the field. Constraining core processes or mantle properties that induce or modulate reversals requires knowing the timing and morphology of field changes that precede and accompany these reversals. But the short duration of transitional field states and fragmentary nature of even the best palaeomagnetic records make it difficult to provide a timeline for the reversal process. 40Ar/39Ar dating of lavas on Tahiti, long thought to record the primary part of the most recent 'Matuyama-Brunhes' reversal, gives an age of 795 +/- 7 kyr, indistinguishable from that of lavas in Chile and La Palma that record a transition in the Earth's magnetic field, but older than the accepted age for the reversal. Only the 'transitional' lavas on Maui and one from La Palma (dated at 776 +/- 2 kyr), agree with the astronomical age for the reversal. Here we propose that the older lavas record the onset of a geodynamo process, which only on occasion would result in polarity change. This initial instability, associated with the first of two decreases in field intensity, began approximately 18 kyr before the actual polarity switch. These data support the claim that complete reversals require a significant period for magnetic flux to escape from the solid inner core and sufficiently weaken its stabilizing effect.

Genomic SELEX is a method for studying the network of nucleic acid-protein interactions within any organism. Here we report the discovery of several interesting and potentially biologically important interactions using genomic SELEX. We have found that bacteriophage MS2 coat protein binds several Escherichia coli mRNA fragments more tightly than it binds the natural, well-studied, phage mRNA site. MS2 coat protein binds mRNA fragments from rffG (involved in formation of lipopolysaccharide in the bacterial outer membrane), ebgR (lactose utilization repressor), as well as from several other genes. Genomic SELEX may yield experimentally induced artifacts, such as molecules in which the fixed sequences participate in binding. We describe several methods (annealing of oligonucleotides complementary to fixed sequences or switching fixed sequences) to eliminate some, or almost all, of these artifacts. Such methods may be useful tools for both randomized sequence SELEX and genomic SELEX.

An increasing number of proteins are being identified that regulate gene expression by binding specific nucleic acidsin vivo. A method termed genomic SELEX facilitates the rapid identification of networks of protein-nucleic acid interactions by identifying within the genomic sequences of an organism the highest affinity sites for any protein of the organism. As with its progenitor, SELEX of random-sequence nucleic acids, genomic SELEX involves iterative binding, partitioning, and amplification of nucleic acids. The two methods differ in that the variable region of the nucleic acid library for genomic SELEX is derived from the genome of an organism. We have used a quick and simple method to construct Escherichia coli, Saccharomyces cerevisiae, and human genomic DNA PCR libraries that can be transcribed with T7 RNA polymerase. We present evidence that the libraries contain overlapping inserts starting at most of the positions within the genome, making these libraries suitable for genomic SELEX.

The SELEX method and oligonucleotide combinatorial chemistry discovery process yields high-affinity/high-specificity ligands for virtually any molecular target. Typically, the enormous starting libraries used in the SELEX process contain 10(14)-10(15) sequences. We now ask if the smaller sequences, complexity of extant organisms, and evolutionary history provide useful interactions between oligonucleotides and at least some unexpected targets. That is, do organisms contain a robust "linkage map" between their oligonucleotides and proteins and/or small molecules that enriches life?

The acidic carboxy-terminal 89-amino acid fragment of bacteriophage T4 gene 32 protein was expressed in Escherichia coli to high levels from an inducible plasmid construct. Infection of induced cells by wild-type T4 phage results in impaired phage DNA synthesis. The time at which DNA synthesis begins and the diminution in DNA synthesis rates correlate with the amount of carboxy-terminal peptide that accumulates intracellularly prior to infection. Correspondingly, when induced cells are infected with viable phage containing a small deletion near the carboxy-terminus of 32 protein (delta PR201), the inhibition of phage DNA synthesis was much more severe. The mutant 32 protein competes less well against overproduced wild-type acid peptide than does wild-type 32 protein. The purified acid peptide, when used as the attached ligand for affinity chromatography, binds several T4 proteins from phage-infected cells, including 43 protein (T4 DNA polymerase), Dda protein (a DNA helicase), and UvsX protein (a Rec-like recombination protein). Furthermore, at 50- to 100-fold molar excess of acid peptide over intact 32 protein, phage DNA synthesis was specifically inhibited at the initiation step in an in vitro 5-protein DNA replication experiment. We propose that one or more phage replication proteins are titrated as non-productive protein-protein complexes at a site away from the DNA template. This implies that the carboxy-terminal domain of 32 protein is involved in an obligate step of replication machine assembly when the protein is properly attached to ssDNA in the vicinity of a primer-template junction. The assembly defect we observe is strikingly similar to the repression, or "squelching", of the activity of certain eukaryotic transcriptional activators.

We have developed an efficient method for the expression of heterologous genes during infection by T4, a bacteriophage known to inhibit the proteolytic systems of Escherichia coli. This system enables us to clone genes in a plasmid expression vector and move them readily into T4. We have used lacZ as a reporter gene to show that both plasmid and phage exhibit low basal expression or high-level expression under the control of a T7 promoter. This system promises a possible solution to the problem of degradation and/or toxicity of overproduced proteins.

We have previously demonstrated that the sequence 5'TGGCAA 3' located at codons 32-33 of the rIIB gene of bacteriophage T4 is a hotspot for transition mutations (Nelson et al. 1981). Here I report the properties of the same TGGCAA sequence introduced into the gene at codons 11-12. The sequence is highly mutable in both locations, suggesting that its high mutability is due to features of the TGGCAA itself and is not dependent on the immediate juxtaposition of additional external sequences. Within this sequence, at either location, only the transition at the central G:C pair frequently arises spontaneously or by 2-aminopurine or ethylmethane sulfonate mutagenesis. However, the 3' G:C pair, in addition, is highly mutable after nitrous acid or hydroxylamine treatment. This suggests that, within the TGGCAA sequence, there are two hotspots which are targeted by different mutagens.

We have sequenced more than 80 mutants of the bacteriophage T4 rIIA and rIIB genes. These include deletions about whose origin we have speculated, mutations affecting the rIIB promoters, various pseudo-revertants of the rII- phenotype, including mutations that bring about the reinitiation of translation following termination, mutations that affect regulation of rIIB translation by regA, the toxic minute plaquing mutants FC237 and FC238 and their detoxifiers, and many more of the classic frameshifts from the Cambridge collection. These mutants have been sequenced using dideoxy-mediated chain termination by either Escherichia coli DNA polymerase using single-stranded DNA as a template or by avian retroviral reverse transcriptase using mRNA or DNA as the template molecule. We list the sequence changes of the mutants with pertinent historic and phenotypic data. The mutants that facilitate translation reinitiation are discussed, and we discuss a model that could account for the generation of many of the mutations.

Deletions and other chromosomal rearrangements can be generated by recombination between repeated sequences. It has been shown in a number of systems that the probability of exchange or gene conversion decreases with increasing distance between repeats. This paper examines the question of how repeats find each other, using deletion formation in bacteriophage T4 as a model system. Homologous sequences adjacent to the repeats can either stimulate or inhibit recombination, depending on their orientation. I present evidence that the spatial separation between repeats is the key determinant of the distance dependence and conclude that adjacent homologous sequences affect recombination by aligning chromosomes so as to position the recombining sites either closer together or farther apart. Analogous examples of apparent 'targeting' by homologous sequences in eukaryotes and other prokaryotes are noted.

The bacteriophage T4 gene regA encodes a protein that diminishes the expression of many unlinked early T4 genes. Previous work demonstrated that regA-mediated repression occurs after transcription. We report here on the identification of the target site on one regA-sensitive mRNA, the message encoding the phage T4 rIIB protein. The target for regA-mediated action overlaps the translational initiation domain of the rIIB messenger. The regA protein may be a repressor that operates translationally on a significant and interesting set of early phage T4 mRNAs.

Homology is an important feature of recombination. We have used the rll cistrons of bacteriophage T4 to determine the extent of homology required for recombination. We varied the amount of homologous DNA available for recombination in both marker rescue experiments and deletion-by-deletion crosses. Our results suggest that the primary pathway for recombination in T4 requires 50 bp of homology. Our finding that recombination is detectable when fewer than 50 bp of homology are available suggests that there is a second, less efficient pathway of recombination in T4. This pathway may be used during the formation of deletions.

We have manipulated the dispensable region of the rIIB gene of bacteriophage T4 in order to study the generation of deletions involving direct repeats. We show that recombination between different parental chromosomes is one source of the deletions we have studied. We have also investigated the effects of structure, base composition and distance on deletion formation. We demonstrate that the potential to form structure in single-stranded DNA has variable effects on the frequency of deletion formation and conclude that, in some cases, slipped mispairing during DNA synthesis can make a substantial contribution to deletion frequencies. The G + C richness of the direct repeats involved in deletion formation is an important parameter of the frequency of deletion formation. We have confirmed that increasing the distance between direct repeats decreases deletion frequency.