Lower visibility of female scientists, compared to male scientists, is a potential reason for the under‐representation of women among senior academic ranks. Visibility in the scientific community ...stems partly from presenting research as an invited speaker at organized meetings. We analysed the sex ratio of presenters at the European Society for Evolutionary Biology (ESEB) Congress 2011, where all abstract submissions were accepted for presentation. Women were under‐represented among invited speakers at symposia (15% women) compared to all presenters (46%), regular oral presenters (41%) and plenary speakers (25%). At the ESEB congresses in 2001–2011, 9–23% of invited speakers were women. This under‐representation of women is partly attributable to a larger proportion of women, than men, declining invitations: in 2011, 50% of women declined an invitation to speak compared to 26% of men. We expect invited speakers to be scientists from top ranked institutions or authors of recent papers in high‐impact journals. Considering all invited speakers (including declined invitations), 23% were women. This was lower than the baseline sex ratios of early‐mid career stage scientists, but was similar to senior scientists and authors that have published in high‐impact journals. High‐quality science by women therefore has low exposure at international meetings, which will constrain Evolutionary Biology from reaching its full potential. We wish to highlight the wider implications of turning down invitations to speak, and encourage conference organizers to implement steps to increase acceptance rates of invited talks.
Rheumatoid arthritis-associated joint pain is frequently observed independent of disease activity, suggesting unidentified pain mechanisms. We demonstrate that antibodies binding to cartilage, ...specific for collagen type II (CII) or cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity in mice, uncoupled from visual, histological and molecular indications of inflammation. Cartilage antibody-induced pain-like behavior does not depend on complement activation or joint inflammation, but instead on tissue antigen recognition and local immune complex (IC) formation. smFISH and IHC suggest that neuronal
and
mRNA are transported to peripheral ends of primary afferents. CII-ICs directly activate cultured WT but not FcRγ chain-deficient DRG neurons. In line with this observation, CII-IC does not induce mechanical hypersensitivity in FcRγ chain-deficient mice. Furthermore, injection of CII antibodies does not generate pain-like behavior in FcRγ chain-deficient mice or mice lacking activating FcγRs in neurons. In summary, this study defines functional coupling between autoantibodies and pain transmission that may facilitate the development of new disease-relevant pain therapeutics.
Hypoaigic zones are aquifer volumes close to and beneath the shores of saline surface water bodies, and are characterized by the presence of time-dependent natural convection and chemical ...stratification. When transient and cyclic processes are involved there is significant potential for complex flow and reaction in the near-shore aquifer, presenting a unique challenge to pollutant risk assessment methodologies. This work considers the nature of some hypoaigic processes generated by the seasonally saline Canning River of Western Australia near a site contaminated by petroleum hydrocarbons. A dissolved hydrocarbon plume migrates within the shallow superficial aquifer to the nearby bank of the Canning River. Beneath the river bank a zone of complex fluid mixing is established by seasonal and tidal influences. Understanding this complexity and the subsequent ramifications for local biogeochemical conditions is critical to inferring the potential for degradation of advecting contaminants. A range of modelling approaches throws light on the overall topographic controls of discharge to the river, on the saline convection processes operating under the river bank, on the potential for fluid mixing, and on the various important time scales in the system. Saline distributions simulated within the aquifer hypoaigic zone are in at least qualitative agreement with previous field measurements at the site and are strongly affected by seasonal influences. Groundwater seepage velocities at the shoreline are found to be positively correlated with river salinity. Calculations of fluid age distributions throughout the system show sensitivity to dispersivity values; however, maximum fluid ages under the river appear to be diffusion limited to a few decades. The saline convection cell in the aquifer defines a zone of strong dispersive dilution of aged (many decades) deep aquifer fluids with relatively young (several months) riverine fluids. Seasonal recharge and river salinity cycles induce regular perturbations to the convection cell, yielding intra-annual variations of 50% in seepage velocity and almost 30% in wedge penetration distance at the plume location.
Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) has been associated with Alzheimer's disease (AD). TREM2 plays a critical role in microglial activation, ...survival, and phagocytosis; however, the pathophysiological role of sTREM2 in AD is not well understood. Understanding the role of sTREM2 in AD may reveal new pathological mechanisms and lead to the identification of therapeutic targets. We performed a genome-wide association study (GWAS) to identify genetic modifiers of CSF sTREM2 obtained from the Alzheimer's Disease Neuroimaging Initiative. Common variants in the membrane-spanning 4-domains subfamily A (
) gene region were associated with CSF sTREM2 concentrations (rs1582763;
= 1.15 × 10
); this was replicated in independent datasets. The variants associated with increased CSF sTREM2 concentrations were associated with reduced AD risk and delayed age at onset of disease. The single-nucleotide polymorphism rs1582763 modified expression of the
and
genes in multiple tissues, suggesting that one or both of these genes are important for modulating sTREM2 production. Using human macrophages as a proxy for microglia, we found that MS4A4A and TREM2 colocalized on lipid rafts at the plasma membrane, that sTREM2 increased with
overexpression, and that silencing of
reduced sTREM2 production. These genetic, molecular, and cellular findings suggest that MS4A4A modulates sTREM2. These findings also provide a mechanistic explanation for the original GWAS signal in the
locus for AD risk and indicate that TREM2 may be involved in AD pathogenesis not only in
risk-variant carriers but also in those with sporadic disease.
An increased prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in children was observed in various diabetes centres worldwide during the COVID-19 pandemic. We aimed to evaluate ...trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes before and during the COVID-19 pandemic, and to identify potential predictors of changes in diabetic ketoacidosis prevalence during the pandemic.
For this international multicentre study, we used data from 13 national diabetes registries (Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA Colorado, and Wales). The study population comprised 104 290 children and adolescents aged 6 months to younger than 18 years, who were diagnosed with type 1 diabetes between Jan 1, 2006, and Dec 31, 2021. The observed diabetic ketoacidosis prevalence in 2020 and 2021 was compared to predictions based on trends over the pre-pandemic years 2006-19. Associations between changes in diabetic ketoacidosis prevalence and the severity of the COVID-19 pandemic and containment measures were examined with excess all-cause mortality in the whole population and the Stringency Index from the Oxford COVID-19 Government Response Tracker.
87 228 children and adolescents were diagnosed with type 1 diabetes between 2006 and 2019, 8209 were diagnosed in 2020, and 8853 were diagnosed in 2021. From 2006 to 2019, diabetic ketoacidosis at diagnosis of type 1 diabetes was present in 23 775 (27·3%) of 87 228 individuals and the mean annual increase in the prevalence of diabetic ketoacidosis in the total cohort from 2006 to 2019 was 1·6% (95% CI 1·3 to 1·9). The adjusted observed prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes was 39·4% (95% CI 34·0 to 45·6) in 2020 and 38·9% (33·6 to 45·0) in 2021, significantly higher than the predicted prevalence of 32·5% (27·8 to 37·9) for 2020 and 33·0% (28·3 to 38·5) for 2021 (p<0·0001 for both years). The prevalence of diabetic ketoacidosis was associated with the pandemic containment measures, with an estimated risk ratio of 1·037 (95% CI 1·024 to 1·051; p<0·0001) per ten-unit increase in the Stringency Index for 2020 and 1·028 (1·009 to 1·047; p=0·0033) for 2021, but was not significantly associated with excess all-cause mortality.
During the COVID-19 pandemic, there was a marked exacerbation of the pre-existing increase in diabetic ketoacidosis prevalence at diagnosis of type 1 diabetes in children. This finding highlights the need for early and timely diagnosis of type 1 diabetes in children and adolescents.
German Federal Ministry for Education and Research, German Robert Koch Institute, German Diabetes Association, German Diabetes Foundation, Slovenian Research Agency, Welsh Government, Central Denmark Region, and Swedish Association of Local Authorities and Regions.
Expressed sequence tag (EST) datasets represent perhaps the largest collection of genetic information. ESTs can be exploited in a variety of biological experiments and analysis. Here we are ...interested in the design of overlapping oligonucleotide (overgo) probes from large unigene (EST-contigs) datasets.
OLIGOSPAWN is a suite of software tools that offers two complementary services, namely (1) the selection of "unique" oligos each of which appears in one unigene but does not occur (exactly or approximately) in any other and (2) the selection of "popular" oligos each of which occurs (exactly or approximately) in as many unigenes as possible. In this paper, we describe the functionalities of OLIGOSPAWN and the computational methods it employs, and we report on experimental results for the overgo probes designed with it.
The algorithms we designed are highly efficient and capable of processing unigene datasets of sizes on the order of several tens of Mb in a few hours on a regular PC. The software has been used to design overgo probes employed to screen a barley BAC library (Hordeum vulgare). OLIGOSPAWN is freely available at http://oligospawn.ucr.edu/.
The human cerebral processing of noxious input from skin and muscle was compared with the use of positron emission tomography with intravenous H2(15)O to detect changes in regional cerebral blood ...flow (rCBF) as an indicator of neuronal activity. During each of eight scans, 11 normal subjects rated the intensity of stimuli delivered to the nondominant (left) forearm on a scale ranging from 0 to 100 with 70 as pain threshold. Cutaneous pain was produced with a high-energy CO2 laser stimulator. Muscle pain was elicited with high-intensity intramuscular electrical stimulation. The mean ratings of perceived intensity for innocuous and noxious stimulation were 32.6 +/- 4.5 (SE) and 78.4 +/- 1.7 for cutaneous stimulation and 15.4 +/- 4.2 and 73.5 +/- 1.4 for intramuscular stimulation. The pain intensity ratings and the differences between noxious and innocuous ratings were similar for cutaneous and intramuscular stimuli (P > 0.05). After stereotactic registration, statistical pixel-by-pixel summation (Z score) and volumes-of-interest (VOI) analyses of subtraction images were performed. Significant increases in rCBF to both noxious cutaneous and intramuscular stimulation were found in the contralateral secondary somatosensory cortex (SII) and inferior parietal lobule Brodmann area (BA) 40. Comparable levels of rCBF increase were found in the contralateral anterior insular cortex, thalamus, and ipsilateral cerebellum. Noxious cutaneous stimulation caused significant activation in the contralateral lateral prefrontal cortex (BA 10/46) and ipsilateral premotor cortex (BA 4/6). Noxious intramuscular stimulation evoked rCBF increases in the contralateral anterior cingulate cortex (BA 24) and subsignificant responses in the contralateral primary sensorimotor cortex (MI/SI) and lenticular nucleus. These activated cerebral structures may represent those recruited early in nociceptive processing because both forms of stimuli were near pain threshold. Correlation analyses showed a negative relationship between changes in rCBF for thalamus and MI/SI for cutaneous stimulation, and positive relationships between thalamus and anterior insula for both stimulus modalities. Direct statistical comparisons between innocuous cutaneous and intramuscular stimulation with the use of Z scores and VOI analyses showed no reliable differences between these two forms of noxious stimulation, indicating a substantial overlap in brain activation pattern. The comparison of noxious cutaneous and intramuscular stimulation indicated more activation in the premotor cortex, SII, and prefrontal cortex with cutaneous stimulation, but these differences did not reach statistical significance. The similar cerebral activation patterns suggest that the perceived differences between acute skin and muscle pain are mediated by differences in the intensity and temporospatial pattern of neuronal activity within similar sets of forebrain structures.
Fentanyl, a mu-opioid receptor agonist, produces analgesia while leaving vibrotactile sensation intact. We used positron emission tomography (PET) to study the mechanisms mediating this specific ...effect in healthy, right-handed human males (ages 18-28 yr). Subjects received either painful cold (n = 11) or painless vibratory (n = 9) stimulation before and after the intravenous injection of fentanyl (1.5 microgram/kg) or placebo (saline). Compared with cool water (29 degrees C), immersion of the hand in ice water (1 degrees C) is painful and produces highly significant increases in regional cerebral blood flow (rCBF) within the contralateral second somatosensory (S2) and insular cortex, bilaterally in the thalamus and cerebellum, and medially in the cerebellar vermis. Responses just below the statistical threshold (3.5 < Z < 4.0) are seen in the contralateral anterior cingulate, ipsilateral insular cortex, and dorsal medial midbrain. The contralateral primary sensory cortex (S1) shows a trend of activation. Except for slight changes in intensity, this pattern is unchanged following a saline placebo injection. Fentanyl reduces the average visual analogue scale ratings of perceived pain intensity (47%) and unpleasantness (50%), reduces pain-related cardioacceleration, and has positive hedonic effects. After fentanyl, but not placebo, all cortical and subcortical responses to noxious cold are greatly reduced. Subtraction analysis (innocuous water + fentanyl) - (innocuous water + no injection) shows that fentanyl alone increases rCBF in the anterior cingulate cortex, particularly in the perigenual region. Vibration (compared with mock vibration) evokes highly significant rCBF responses in the contralateral S1 cortex in the baseline (no injection) and placebo conditions; borderline responses (3.5 < Z < 4. 0) are detected also in the contralateral thalamus. Fentanyl has no effect on the perceived intensity or unpleasantness of vibratory stimulation, which continues to activate contralateral S1. Fentanyl alone (mock vibration + fentanyl) - (mock vibration + no injection) again produces highly significant activation of the perigenual and mid-anterior cingulate cortex. A specific comparison of volumes of interest, developed from activation peaks in the baseline condition (no injection), shows that fentanyl strongly attenuates both the contralateral thalamic and S1 cortical responses to noxious cold stimulation (P < 0.048 and 0.007, respectively) but fails to affect significantly these responses to vibrotactile stimulation (P > 0.26 and 0.91, respectively). In addition, fentanyl, compared with placebo, produces a unique activation of the mid-anterior cingulate cortex during fentanyl analgesia, suggesting that this region of the cingulate cortex participates actively in mediating opioid analgesia. The results are consistent with a selective, fentanyl-mediated suppression of nociceptive spinothalamic transmission to the forebrain. This effect could be implemented directly at the spinal level, indirectly through cingulate corticofugal pathways, or by a combination of both mechanisms.
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