Large areas of cold hypoxic water occur as distinct strata in the eastern tropical Pacific (ETP) and Atlantic oceans as a result of high productivity initiated by intense nutrient upwelling. We show ...that this stratum restricts the depth distribution of tropical pelagic marlins, sailfish, and tunas by compressing the acceptable physical habitat into a narrow surface layer. This layer extends downward to a variable boundary defined by a shallow thermocline, often at 25 m, above a barrier of cold hypoxic water. The depth distributions of marlin and sailfish monitored with electronic tags and average dissolved oxygen (DO) and temperature profiles show that this cold hypoxic environment constitutes a lower habitat boundary in the ETP, but not in the western North Atlantic (WNA), where DO is not limiting. Eastern Pacific and eastern Atlantic sailfish are larger than those in WNA, where the hypoxic zone is much deeper or absent. Larger sizes may reflect enhanced foraging opportunities afforded by the closer proximity of predator and prey in compressed habitat, as well as by the higher productivity. The shallow band of acceptable habitat restricts these fishes to a very narrow surface layer and makes them more vulnerable to over‐exploitation by surface gears. Predictably, the long‐term landings of tropical pelagic tunas from areas of habitat compression have been far greater than in surrounding areas. Many tropical pelagic species in the Atlantic Ocean are currently either fully exploited or overfished and their future status could be quite sensitive to increased fishing pressures, particularly in areas of habitat compression.
Simulated size–age observations were collected from hypothetical populations with known growth to quantify potential bias in estimates of growth and mortality that can result from size‐selective ...sampling. The population lengths at ages were normally distributed around means predicted by published von Bertalanffy (VB) equations for the Striped Marlin Kajikia audax or Vermilion Snapper Rhomboplites aurorubens. Parameter estimates for the VB equation were accurate when the data were collected with random and age‐stratified sampling. Size‐stratified sampling caused important bias in estimates of length at age and fitted VB parameters. The bias increased with the coefficient of variation of mean size at age and total mortality. It became more severe when sampling effort was increased to compensate for low sample numbers in bins within the upper tail of the distribution of sizes in the populations. Error occasionally exceeded 100% for asymptotic length L∞ and 50% for the Brody growth coefficient K. When a random sample was supplemented with ≤10% large fish, the bias was sometimes greater than that observed when a completely size‐stratified design was used. Such error could corrupt the reliability of analyses that depend on VB parameters. For Striped Marlins, natural mortality computed with the Pauly (1980) equation using results from length‐selective sampling strategies often deviated 50% or more from the values predicted using the “true” growth coefficients. Potential for nonrepresentative sampling of lengths at age should be routinely described when VB models are first published and should be considered whenever the growth estimates are later used for other purposes.
Increasing antibiotic resistance among pathogenic bacterial species is a serious public health problem and has prompted research examining the antibacterial effects of alternative compounds and novel ...treatment strategies. Compounding this problem is the ability of many pathogenic bacteria to form biofilms during chronic infections. Importantly, these communities are often recalcitrant to antibiotic treatments that show effectiveness against acute infection. The antimicrobial properties of silver have been known for decades, but recently silver and silver-containing compounds have seen renewed interest as antimicrobial agents for treating bacterial infections. The goal of this study was to assess the ability of citrate-capped silver nanoparticles (AgNPs) of various sizes, alone and in combination with the aminoglycoside antibiotic tobramycin, to inhibit established
biofilms. Our results demonstrate that smaller 10-nm and 20-nm AgNPs were more effective at synergistically potentiating the activity of tobramycin. Visualization of biofilms treated with combinations of 10-nm AgNPs and tobramycin reveals that the synergistic bactericidal effect may be caused by disrupting cellular membranes. Minimum biofilm eradication concentration (MBEC) assays using clinical
isolates shows that small AgNPs are more effective than larger AgNPs at inhibiting biofilms, but that the synergy effect is likely a strain-dependent phenomenon. These data suggest that small AgNPs synergistically potentiate the activity of tobramycin against
and may reveal a potential role for AgNP/antibiotic combinations in treating patients with chronic infections in a strain-specific manner.
Oxygen minimum zones (OMZs) below near‐surface optimums in the eastern tropical seas are among the largest contiguous areas of naturally occurring hypoxia in the world oceans, and are predicted to ...expand and shoal with global warming. In the eastern tropical Pacific (ETP), the surface mixed layer is defined by a shallow thermocline above a barrier of cold hypoxic water, where dissolved oxygen levels are ≤3.5 mL L−1. This thermocline (∼25–50 m) constitutes a lower hypoxic habitat boundary for high oxygen demand tropical pelagic billfish and tunas (i.e., habitat compression). To evaluate similar oceanographic conditions found in the eastern tropical Atlantic (ETA), we compared vertical habitat use of 32 sailfish (Istiophorus platypterus) and 47 blue marlin (Makaira nigricans) monitored with pop‐up satellite archival tags in the ETA and western North Atlantic (WNA). Both species spent significantly greater proportions of their time in near‐surface waters when inside the ETA than when in the WNA. We contend that the near‐surface density of billfish and tunas increases as a consequence of the ETA OMZ, therefore increasing their vulnerability to overexploitation by surface gears. Because the ETA OMZ encompasses nearly all Atlantic equatorial waters, the potential impacts of overexploitation are a concern. Considering the obvious differences in catchability inside and outside the compression zones, it seems essential to standardize these catch rates separately to minimize inaccuracies in stock assessments for these species. This is especially true in light of global warming, which will likely exacerbate future compression impacts.
A carbon-rich black layer, dating to almost equal to12.9 ka, has been previously identified at almost equal to50 Clovis-age sites across North America and appears contemporaneous with the abrupt ...onset of Younger Dryas (YD) cooling. The in situ bones of extinct Pleistocene megafauna, along with Clovis tool assemblages, occur below this black layer but not within or above it. Causes for the extinctions, YD cooling, and termination of Clovis culture have long been controversial. In this paper, we provide evidence for an extraterrestrial (ET) impact event at congruent with12.9 ka, which we hypothesize caused abrupt environmental changes that contributed to YD cooling, major ecological reorganization, broad-scale extinctions, and rapid human behavioral shifts at the end of the Clovis Period. Clovis-age sites in North American are overlain by a thin, discrete layer with varying peak abundances of (i) magnetic grains with iridium, (ii) magnetic microspherules, (iii) charcoal, (iv) soot, (v) carbon spherules, (vi) glass-like carbon containing nanodiamonds, and (vii) fullerenes with ET helium, all of which are evidence for an ET impact and associated biomass burning at almost equal to12.9 ka. This layer also extends throughout at least 15 Carolina Bays, which are unique, elliptical depressions, oriented to the northwest across the Atlantic Coastal Plain. We propose that one or more large, low-density ET objects exploded over northern North America, partially destabilizing the Laurentide Ice Sheet and triggering YD cooling. The shock wave, thermal pulse, and event-related environmental effects (e.g., extensive biomass burning and food limitations) contributed to end-Pleistocene megafaunal extinctions and adaptive shifts among PaleoAmericans in North America.
Patients with rheumatoid arthritis (RA) experience extra-articular manifestations including osteoporosis and muscle wasting, which closely associate with severity of disease. Whilst therapeutic ...glucocorticoids (GCs) reduce inflammation in RA, their actions on muscle and bone metabolism in the context of chronic inflammation remain unclear. We utilised the TNF-tg model of chronic polyarthritis to ascertain the impact of therapeutic GCs on bone and muscle homeostasis in the context of systemic inflammation.
TNF-tg and wild-type (WT) animals received either vehicle or the GC corticosterone (100 μg/ml) in drinking water at onset of arthritis. Arthritis severity and clinical parameters were measured, serum collected for ELISA and muscle and bone biopsies collected for μCT, histology and mRNA analysis. In vivo findings were examined in primary cultures of osteoblasts, osteoclasts and myotubes.
TNF-tg mice receiving GCs showed protection from inflammatory bone loss, characterised by a reduction in serum markers of bone resorption, osteoclast numbers and osteoclast activity. In contrast, muscle wasting was markedly increased in WT and TNF-tg animals receiving GCs, independently of inflammation. This was characterised by a reduction in muscle weight and fibre size, and an induction in anti-anabolic and catabolic signalling.
This study demonstrates that when given in early onset chronic polyarthritis, oral GCs partially protect against inflammatory bone loss, but induce marked muscle wasting. These results suggest that in patients with inflammatory arthritis receiving GCs, the development of interventions to manage deleterious side effects in muscle should be prioritised.
Abstract
Background
Coronavirus disease-19 (COVID-19) infection causes persistent health problems such as breathlessness, chest pain and fatigue, and therapies for the prevention and early treatment ...of post-COVID-19 syndromes are needed. Accordingly, we are investigating the effect of a resistance exercise intervention on exercise capacity and health status following COVID-19 infection.
Methods
A two-arm randomised, controlled clinical trial including 220 adults with a diagnosis of COVID-19 in the preceding 6 months. Participants will be classified according to clinical presentation: Group A, not hospitalised due to COVID but persisting symptoms for at least 4 weeks leading to medical review; Group B, discharged after an admission for COVID and with persistent symptoms for at least 4 weeks; or Group C, convalescing in hospital after an admission for COVID.
Participants will be randomised to usual care or usual care plus a personalised and pragmatic resistance exercise intervention for 12 weeks. The primary outcome is the incremental shuttle walks test (ISWT) 3 months after randomisation with secondary outcomes including spirometry, grip strength, short performance physical battery (SPPB), frailty status, contacts with healthcare professionals, hospitalisation and questionnaires assessing health-related quality of life, physical activity, fatigue and dyspnoea.
Discussion
Ethical approval has been granted by the National Health Service (NHS) West of Scotland Research Ethics Committee (REC) (reference: GN20CA537) and recruitment is ongoing. Trial findings will be disseminated through patient and public forums, scientific conferences and journals.
Trial registration
ClinicialTrials.gov
NCT04900961
. Prospectively registered on 25 May 2021
Joint injury involving destabilisation of the joint and damage to the articular cartilage (e.g., sports-related injury) can result in accelerated post-traumatic osteoarthritis (PTOA). Destabilised ...medial meniscotibial ligament (DMM) surgery is one of the most commonly used murine models and whilst it recapitulates Osteoarthritis (OA) pathology, it does not necessarily result in multi-tissue injury, as occurs in PTOA. We hypothesised that simultaneous cartilage damage and joint destabilisation would accelerate the onset of OA pathology.
OA was induced in C57BL/6 mice via (a) DMM, (b) microblade scratches of articular cartilage (CS) or (c) combined DMM and cartilage scratch (DCS). Mice were culled 7, 14 and 28 days post-surgery. Microcomputed tomography (μCT) and histology were used to monitor bone changes and inflammation. Dynamic weight bearing, an indirect measure of pain, was assessed on day 14.
Osteophytogenesis analysis via μCT revealed that osteophytes were present in all groups at days 7 and 14 post-surgery. However, in DCS, osteophytes were visually larger and more numerous when compared with DMM and cartilage scratch (CS). Histological assessment of cartilage at day 14 and 28, revealed significantly greater damage in DCS compared with DMM and CS. Furthermore, a significant increase in synovitis was observed in DCS. Finally, at day 14 osteophyte numbers correlated with changes in dynamic weight bearing.
Joint destabilisation when combined with simultaneous cartilage injury accelerates joint deterioration, as seen in PTOA. Thus, DCS provides a novel and robust model for investigating multiple pathological hallmarks, including osteophytogenesis, cartilage damage, synovitis and OA-related pain.
In Escherichia coli, formation of new cells is mediated by the elongasome and divisome that govern cell elongation and septation, respectively. Proper transition between these events is essential to ...ensure viable progeny are produced; however, the components of each complex responsible for transmission of the cell signal to shift from elongation to septation are unclear. Recently, a region within the N-terminal domain of the essential divisome protein FtsK (FtsK
) was identified that points to a key role for FtsK as a checkpoint of cell envelope remodeling during division. Here, we used site-specific in vivo UV cross-linking to probe the periplasmic loops of FtsK
for protein interaction partners critical for FtsK
function. Mass spectrometry analysis of five unique FtsK
periplasmic cross-links revealed a network of potential FtsK
interactors, one of which included the septal peptidoglycan binding protein rare lipoprotein A (RlpA). This protein was further verified as a novel interaction partner of FtsK
by an in vitro pull-down assay. Deletion of rlpA from an FtsK temperature-sensitive E. coli strain partially restored cell growth and largely suppressed cellular filamentation compared to the wild-type strain. This suggests that interaction with RlpA may be critical in suppressing septation until proper assembly of the divisome.
Previous immunological studies in the eastern USA have failed to establish a direct connection between Paleoamericans and extinct megafauna species. The lack of physical evidence for the presence of ...extinct megafauna begs the question, did early Paleoamericans regularly hunt or scavenge these animals, or were some megafauna already extinct? In this study of 120 Paleoamerican stone tools from across North and South Carolina, we investigate this question using crossover immunoelectrophoresis (CIEP). We find immunological support for the exploitation of extant and extinct megafauna, including Proboscidea, Equidae, and Bovidae (possibly Bison antiquus), on Clovis points and scrapers, as well as possible early Paleoamerican Haw River points. Post-Clovis points tested positive for Equidae and Bovidae but not Proboscidea. Microwear results are consistent with projectile usage, butchery, fresh- and dry hide scraping, the use of ochre-coated dry hides for hafting, and dry hide sheath wear. This study represents the first direct evidence of the exploitation of extinct megafauna by Clovis and other Paleoamerican cultures in the Carolinas and more broadly, across the eastern United States, where there is generally poor to non-existent faunal preservation. Future CIEP analysis of stone tools may provide evidence on the timing and demography of megafaunal collapse leading to eventual extinction.