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.
Genomic instability and high mutation rates cause cancer to acquire numerous mutations and chromosomal alterations during its somatic evolution; most are termed passengers because they do not confer ...cancer phenotypes. Evolutionary simulations and cancer genomic studies suggest that mildly deleterious passengers accumulate and can collectively slow cancer progression. Clinical data also suggest an association between passenger load and response to therapeutics, yet no causal link between the effects of passengers and cancer progression has been established. To assess this, we introduced increasing passenger loads into human cell lines and immunocompromised mouse models. We found that passengers dramatically reduced proliferative fitness (∼3% per Mb), slowed tumor growth, and reduced metastatic progression. We developed new genomic measures of damaging passenger load that can accurately predict the fitness costs of passengers in cell lines and in human breast cancers. We conclude that genomic instability and an elevated load of DNA alterations in cancer is a double-edged sword: it accelerates the accumulation of adaptive drivers, but incurs a harmful passenger load that can outweigh driver benefit. The effects of passenger alterations on cancer fitness were unrelated to enhanced immunity, as our tests were performed either in cell culture or in immunocompromised animals. Our findings refute traditional paradigms of passengers as neutral events, suggesting that passenger load reduces the fitness of cancer cells and slows or prevents progression of both primary and metastatic disease. The antitumor effects of chemotherapies can in part be due to the induction of genomic instability and increased passenger load.
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Many aspects of photoperception by plants and microorganisms are initiated by the phytochrome (Phy) family of photoreceptors that detect light through interconversion between red light- (Pr) and ...far-red light-absorbing (Pfr) states. Plants synthesize a small family of Phy isoforms (PhyA to PhyE) that collectively regulate photomorphogenesis and temperature perception through redundant and unique actions. While the selective roles of these isoforms have been partially attributed to their differing abundances, expression patterns, affinities for downstream partners, and turnover rates, we show here from analysis of recombinant
chromoproteins that the Phy isoforms also display distinct biophysical properties. Included are a hypsochromic shift in the Pr absorption for PhyC and varying rates of Pfr to Pr thermal reversion, part of which can be attributed to the core photosensory module in each. Most strikingly, PhyB combines strong temperature dependence of thermal reversion with an order-of-magnitude faster rate to likely serve as the main physiological thermosensor, whereby thermal reversion competes with photoconversion. In addition, comparisons of Pfr occupancies for PhyA and PhyB under a range of red- and white-light fluence rates imply that low-light environments are effectively sensed by PhyA, while high-light environments, such as full sun, are effectively sensed by PhyB. Parallel analyses of the Phy isoforms from potato and maize showed that the unique features within the
family are conserved, thus indicating that the distinct biophysical properties among plant Phy isoforms emerged early in Phy evolution, likely to enable full interrogation of their light and temperature environments.
Surgical reconstruction of the anterior cruciate ligament (ACL) and subsequent physical therapy can help athletes return to competition; however, re-injury rates remain disproportionately high due, ...in part, to lingering biomechanical and neurological factors that are not fully addressed during rehabilitation. Prior reports indicate that individuals exhibit altered electrical activity in both brain and muscle after ACL reconstruction (ACLR). In this investigation, we aimed to extend existing approaches by introducing a novel non-linear analysis of corticomuscular dynamics, which does not assume oscillatory coupling between brain and muscle: Corticomuscular cross-recurrence analysis (CM-cRQA). Our findings indicate that corticomuscular dynamics vary significantly between involved (injured) and uninvolved legs of participants with ACLR during voluntary isometric contractions between the brain and both the vastus medialis and lateralis. This finding points to a potential lingering neural deficit underlying re-injury for athletes after surgical reconstruction, namely the dynamical structure of neuromuscular (brain to quad muscle) coordination, which is significantly asymmetric, between limbs, in those who have ACLR.
Emissions from flooded land represent a direct source of anthropogenic greenhouse gas (GHG) emissions. Methane emissions from large, artificial water bodies have previously been considered, with ...numerous studies assessing emission rates and relatively simple procedures available to determine their surface area and generate upscaled emissions estimates. In contrast, the role of small artificial water bodies (ponds) is very poorly quantified, and estimation of emissions is constrained both by a lack of data on their spatial extent and a scarcity of direct flux measurements. In this study, we quantified the total surface area of water bodies < 105 m2 across Queensland, Australia, and emission rates from a variety of water body types and size classes. We found that the omission of small ponds from current official land use data has led to an underestimate of total flooded land area by 24 %, of small artificial water body surface area by 57 % and of the total number of artificial water bodies by 1 order of magnitude. All studied ponds were significant hotspots of methane production, dominated by ebullition (bubble) emissions. Two scaling approaches were developed with one based on pond primary use (stock watering, irrigation and urban lakes) and the other using size class. Both approaches indicated that ponds in Queensland alone emit over 1.6 Mt CO2 eq. yr−1, equivalent to 10 % of the state's entire land use, land use change and forestry sector emissions. With limited data from other regions suggesting similarly large numbers of ponds, high emissions per unit area and under-reporting of spatial extent, we conclude that small artificial water bodies may be a globally important missing source of anthropogenic greenhouse gas emissions.
Impaired corticomotor function arising from altered intracortical and corticospinal pathways are theorized to impede muscle recovery following anterior cruciate ligament (ACL) surgery, yet functional ...implications of centrally driven adaptations remain unclear. We aimed to assess relationships between quadriceps corticomotor and neuromechanical function after ACL surgery, and to compare with contralateral and control limbs. 16 individuals after primary, unilateral ACL surgery and 16 sex- and age-matched controls participated. Corticomotor function was assessed using transcranial magnetic stimulation, and quantified via active motor thresholds (AMT), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF). Neuromechanical function was quantified via electromechanical delay, early and late-phase rate of torque development (RTD
0–50
, RTD
100–200
), coefficient of variation, maximal voluntary isometric contraction (MVIC) torque, and central activation ratio. We observed significant correlations in the ACL limbs between: AMT and RTD
0–50
(
r
= − 0.513,
p
= 0.031), SICI and RTD
100–200
(
r
= 0.501,
p
= 0.048), AMT and SICI (
r
= − 0.659,
p
= 0.010), AMT and ICF (
r
= 0.579,
p
= 0.031), RTD
0–50
and MVIC (
r
= 0.504,
p
= 0.023), and RTD
100–200
and MVIC (
r
= 0.680,
p
= 0.002). The ACL limbs demonstrated higher AMT compared to controls (44.9 ± 8.4 vs. 30.1 ± 8.2%,
p
< 0.001), and lesser MVIC torque (2.37 ± 0.52 vs. 2.80 ± 0.59 Nm/kg,
p
= 0.005) and RTD
100–200
(6.79 ± 1.72 vs. 7.90 ± 1.98 Nm/kg/s,
p
= 0.006) compared to the contralateral limbs. Our findings indicate that lesser corticospinal excitability is associated with lesser early-phase RTD, and greater intracortical inhibition is associated with lesser late-phase RTD. These findings provide evidence of implications of altered intracortical and corticospinal pathways relative to the ability to rapidly generate quadriceps torque following ACL surgery.
Objective:
The cellular and molecular mechanisms underlying magnetic resonance imaging‐defined white matter (WM) changes associated with age‐related cognitive decline remain poorly defined. We tested ...the hypothesis that WM lesions in older adults, defined by diffusion tensor imaging (DTI), arise in the setting of vascular brain injury (VBI) and are characterized by increased free radical injury and aberrant oligodendrocyte lineage (OL) cell response to injury.
Methods:
We undertook a multimodal analysis of prefrontal cortex (PFC) WM from 25 autopsies derived from a population‐based cohort where VBI and Alzheimer disease (AD) frequently coincide. Ex vivo high field strength DTI measurements of fractional anisotropy (FA), apparent diffusion coefficient, and axial and radial (D⊥) diffusivity were measured at high magnetic field strength (11.7T) and analyzed relative to quantitative in vivo biomarkers of free radical injury, an OL‐specific marker Olig2, and histologic evaluation of hyaluronan (HA), an inhibitor of OL maturation.
Results:
Coincident AD and VBI showed significant association with lower FA and a robust relationship between decreasing FA and increasing D⊥. Free radical injury to docosahexaenoate and adrenate in PFC WM was significantly elevated in cases with VBI independent of AD, and was inversely correlated with FA. Similarly, increased density of Olig2‐immunoreactive cells in PFC WM was significantly associated with VBI independent of AD and colocalized with regions enriched in HA.
Interpretation:
DTI‐defined PFC WM lesions in older individuals are characterized by free radical injury to myelin and neuroaxonal elements that coincides with pronounced expansion of the pool of OL cells in HA‐rich regions. ANN NEUROL 2011;70: 465–476.
Purpose
The purpose of this investigation was to compare the quality of neural drive and recruited quadriceps motor units’ (MU) action potential amplitude (MUAP
AMP
) and discharge rate (mean firing ...rate (MFR)) relative to recruitment threshold (RT) between individuals with anterior cruciate ligament reconstruction (ACLR) and controls.
Methods
Fourteen individuals with ACLR and 13 matched controls performed trapezoidal knee extensor contractions at 30%, 50%, 70%, and 100% of their maximal voluntary isometric contraction (MVIC). Decomposition electromyography (dEMG) and torque were recorded concurrently. The Hoffmann reflex (H-reflex) and central activation ratio (CAR) were acquired bilaterally to detail the proportion of MU pool available and volitionally activated. We examined MUAP
AMP
-RT and MFR-RT relationships with linear regression and extracted the regression line slope, y-intercept, and RT range for each contraction. Linear mixed effect modelling used to analyze the effect of group and limb on regression line slope and RT range.
Results
Individuals with ACLR demonstrated lower MVIC torque in the involved limb compared to uninvolved limb. There were no differences in H-reflex or CAR between groups or limbs. The ACLR involved limb demonstrated smaller mass-normalized RT range and slower MU firing rates at high contraction intensities (70% and 100% MVIC) compared to uninvolved and control limbs. The ACLR involved limb also demonstrated larger MU action potentials in the VM compared to the contralateral limb. These differences were largely attenuated with relative RT normalization.
Conclusions
These results suggest that persistent strength deficits following ACLR may be attributable to a diminished quadriceps motor neuron pool and inability to upregulate the firing rate of recruited MUs.
Thoracic outlet syndrome (TOS) can be a career-threatening injury for Major League Baseball (MLB) pitchers, often requiring surgical management. The purpose of this study is to determine the efficacy ...of surgical management for TOS as a function of return to play and quantitative pitching metrics.
27 MLB pitchers underwent surgical treatment for TOS between January 2001 and December 2017. Analysis of pre and postoperative pitching metrics were used to assess the effect of surgery on 20 pitchers who returned to pitch in MLB. All pitching metrics were compared via assessing performance two years prior to surgery and two years after surgery. For 20 pitchers who returned to pitch, MLB pitching metrics of earned run average (ERA), walks plus hits per innings pitched (WHIP), wins above replacement (WAR), and average fastball velocity were used to assess a pitcher's ability to return to preoperative performance level.
Of the 27 pitchers, 20 pitchers were diagnosed with neurogenic thoracic outlet syndrome (NTOS) and seven with venous thoracic outlet syndrome (VTOS). The average age of onset of TOS was 28.6 years. There was no significant difference between the age of onset between the NTOS and VTOS populations (p = 0.272). Of the 27 pitchers, 20 (74.1%) were able to return to MLB play at a mean of 297 days (range, 105-638 days) after surgery. Pitching metrics demonstrated that pitcher ERA remained inferior postoperatively compared to baseline preoperative performance (3.66 vs 4.50, p = 0.03). Fastball velocity (p = 0.94) and strike percentage (p = 0.50) were equivalent to pre-injury performance.
74% of professional pitchers who undergo surgical intervention for TOS are able to return to play at the MLB level. With regards to performance, the majority of metrics were unchanged from prior to surgery, indicating return at a similar functional level.
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