Bornean orangutan mandibular morphology has been functionally linked to the exploitation of hard and tough foods, based on evidence that Pongo pygmaeus wurmbii spends a greater percentage of time ...feeding on bark, seeds and vegetation compared with Pongo abelii (Sumatran orangutans) and the assumption that these tissues are more challenging to process than fruit pulp. We measured and compared toughness (R) and Young's modulus (E) of ripe and unripe foods exploited by P. abelii and P. p. wurmbii. Additionally, we recorded and compared the percentage of time these orangutans fed on plants/plant parts of varying degrees of R and E. Compared with P. abelii, P. p. wurmbii consumed significantly tougher and more displacement limited (R/E)0.5 fruit parts, leaves and inner bark, and spent a significantly greater percentage of time feeding on immature leaves, unripe fruit and other vegetation. Modulus did not vary as expected between species, likely because we failed to capture the high-end range of modulus values for tissues consumed by P. p. wurmbii. Notably, P. p. wurmbii spent ∼40% of its feeding time on the toughest foods consumed (between 1000 and 4000 J m−2). Thus, the hypothesis that mandibular robusticity in P. p. wurmbii is functionally linked to feeding on tough foods is supported and is likely related to countering relatively larger external forces and/or repetitive loads required to process the toughest tissues. The importance of elastic modulus on morphological divergence awaits future studies capturing the full range of this material property for P. p. wurmbii. Finally, phenophase and fruit availability influence orangutan species differences in food material properties and percentage of time spent feeding on various foods, emphasizing the importance of incorporating these variables in future studies of feeding ecology and craniodental morphology in extant taxa.
Abstract
O
-Acetylation of the capsular polysaccharide (CPS) of
Neisseria meningitidis
serogroup A (NmA) is critical for the induction of functional immune responses, making this modification ...mandatory for CPS-based anti-NmA vaccines. Using comprehensive NMR studies, we demonstrate that
O
-acetylation stabilizes the labile anomeric phosphodiester-linkages of the NmA-CPS and occurs in position C3 and C4 of the
N
-acetylmannosamine units due to enzymatic transfer and non-enzymatic ester migration, respectively. To shed light on the enzymatic transfer mechanism, we solved the crystal structure of the capsule
O
-acetyltransferase CsaC in its apo and acceptor-bound form and of the CsaC-H228A mutant as trapped acetyl-enzyme adduct in complex with CoA. Together with the results of a comprehensive mutagenesis study, the reported structures explain the strict regioselectivity of CsaC and provide insight into the catalytic mechanism, which relies on an unexpected Gln-extension of a classical Ser-His-Asp triad, embedded in an α/β-hydrolase fold.
Background The Nod-like receptor NACHT, LRR, and PYD domain–containing protein 3 (NLRP3) and Bruton tyrosine kinase (BTK) are protagonists in innate and adaptive immunity, respectively. NLRP3 senses ...exogenous and endogenous insults, leading to inflammasome activation, which occurs spontaneously in patients with Muckle-Wells syndrome; BTK mutations cause the genetic immunodeficiency X-linked agammaglobulinemia (XLA). However, to date, few proteins that regulate NLRP3 inflammasome activity in human primary immune cells have been identified, and clinically promising pharmacologic targeting strategies remain elusive. Objective We sought to identify novel regulators of the NLRP3 inflammasome in human cells with a view to exploring interference with inflammasome activity at the level of such regulators. Methods After proteome-wide phosphoproteomics, the identified novel regulator BTK was studied in human and murine cells by using pharmacologic and genetic BTK ablation. Results Here we show that BTK is a critical regulator of NLRP3 inflammasome activation: pharmacologic (using the US Food and Drug Administration–approved inhibitor ibrutinib) and genetic (in patients with XLA and Btk knockout mice) BTK ablation in primary immune cells led to reduced IL-1β processing and secretion in response to nigericin and the Staphylococcus aureus toxin leukocidin AB (LukAB). BTK affected apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and caspase-1 cleavage and interacted with NLRP3 and ASC. S aureus infection control in vivo and IL-1β release from cells of patients with Muckle-Wells syndrome were impaired by ibrutinib. Notably, IL-1β processing and release from immune cells isolated from patients with cancer receiving ibrutinib therapy were reduced. Conclusion Our data suggest that XLA might result in part from genetic inflammasome deficiency and that NLRP3 inflammasome–linked inflammation could potentially be targeted pharmacologically through BTK.
A major fraction of atmospheric aerosol particles, which affect both air quality and climate, form from gaseous precursors in the atmosphere. Highly oxygenated organic molecules (HOMs), formed by ...oxidation of biogenic volatile organic compounds, are known to participate in particle formation and growth. However, it is not well understood how they interact with atmospheric pollutants, such as nitrogen oxides (NO
) and sulfur oxides (SO
) from fossil fuel combustion, as well as ammonia (NH
) from livestock and fertilizers. Here, we show how NO
suppresses particle formation, while HOMs, sulfuric acid, and NH
have a synergistic enhancing effect on particle formation. We postulate a novel mechanism, involving HOMs, sulfuric acid, and ammonia, which is able to closely reproduce observations of particle formation and growth in daytime boreal forest and similar environments. The findings elucidate the complex interactions between biogenic and anthropogenic vapors in the atmospheric aerosol system.
Objectives
Although fermented food use is ubiquitous in humans, the ecological and evolutionary factors contributing to its emergence are unclear. Here we investigated the ecological contexts ...surrounding the consumption of fruits in the late stages of fermentation by wild primates to provide insight into its adaptive function. We hypothesized that climate, socioecological traits, and habitat patch size would influence the occurrence of this behavior due to effects on the environmental prevalence of late‐stage fermented foods, the ability of primates to detect them, and potential nutritional benefits.
Materials and methods
We compiled data from field studies lasting at least 9 months to describe the contexts in which primates were observed consuming fruits in the late stages of fermentation. Using generalized linear mixed‐effects models, we assessed the effects of 18 predictor variables on the occurrence of fermented food use in primates.
Results
Late‐stage fermented foods were consumed by a wide taxonomic breadth of primates. However, they generally made up 0.01%–3% of the annual diet and were limited to a subset of fruit species, many of which are reported to have mechanical and chemical defenses against herbivores when not fermented. Additionally, late‐stage fermented food consumption was best predicted by climate and habitat patch size. It was more likely to occur in larger habitat patches with lower annual mean rainfall and higher annual mean maximum temperatures.
Discussion
We posit that primates capitalize on the natural fermentation of some fruits as part of a nutritional strategy to maximize periods of fruit exploitation and/or access a wider range of plant species. We speculate that these factors contributed to the evolutionary emergence of the human propensity for fermented foods.
Wild primates consuming fermented fruits.
American Association of Physical Anthropologists (AAPA) membership surveys from 1996 and 1998 revealed significant gender disparities in academic status. A 2014 follow‐up survey showed that gender ...equality had improved, particularly with respect to the number of women in tenure‐stream positions. However, although women comprised 70% of AAPA membership at that time, the percentage of women full professors remained low. Here, we continue to consider the status of women in biological anthropology by examining the representation of women through a quantitative analysis of their participation in annual meetings of the AAPA during the past 20 years. We also review the programmatic goals of the AAPA Committee on Diversity Women's Initiative (COD‐WIN) and provide survey results of women who participated in COD‐WIN professional development workshops. Finally, we examine the diversity of women's career paths through the personal narratives of 14 women biological anthropologists spanning all ranks from graduate student to Professor Emeritus. We find that over the past 20 years, the percentage of women first authors of invited symposia talks has increased, particularly in the sub‐disciplines of bioarchaeology, genetics, and paleoanthropology. The percentage of women first authors on contributed talks and posters has also increased. However, these observed increases are still lower than expected given the percentage of graduate student women and women at the rank of assistant and associate professor. The personal narratives highlight first‐hand the impact of mentoring on career trajectory, the challenges of achieving work‐life satisfaction, and resilience in the face of the unexpected. We end with some suggestions for how to continue to improve equality and equity for women in biological anthropology.
Numerous comparative studies have sought to demonstrate a functional link between feeding behavior, diet, and mandibular form in primates. In lieu of data on the material properties of foods ingested ...and masticated, many investigators have relied on qualitative dietary classifications such as “folivore” or “frugivore.” Here we provide the first analysis of the relationship between jaw form, dietary profiles, and food material properties in large-bodied hominoids. We employed ratios of area moments of inertia and condylar area to estimate moments imposed on the mandible in order to evaluate and compare the relative ability to counter mandibular loads among central Bornean orangutans (
Pongo pygmaeus wurmbii), Virunga mountain gorillas (
Gorilla beringei beringei), and east African chimpanzees (
Pan troglodytes schweinfurthii). We used data on elastic modulus (
E) of fruit, fracture toughness (
R) of fruit, leaves, and non-fruit, non-leaf vegetation, and derived fragmentation indices (√
R/
E and √
ER), as proxies for bite force. We generated bending and twisting moments (force
×
moment arm) for various mandibular loading behaviors using food material properties to estimate minimally required bite forces. Based on
E and
R of foods ingested and masticated, we hypothesized improved resistance to mandibular loads in
Pongo p.
wurmbii compared to the African apes, and in
G. b. beringei compared to
Pan t. schweinfurthii. Results reveal that our predictions are borne out only when bite forces are estimated from maximum
R of non-fruit, non-leaf vegetation. For all other tissues and material properties results were contrary to our predictions. Importantly, as food material properties change, the moments imposed on the mandible change; this, in turn, alters the entire ratio of relative load resistance to moment. The net effect is that species appear over- or under-designed for the moments imposed on the mandible. Our hypothesis, therefore, is supported only if we accept that maximum
R of these vegetative tissues represents the relevant mechanical property influencing the magnitude of neuromuscular activity, food fragmentation, and mandibular morphology. A general implication is that reliable estimates of average and maximum bite forces from food material properties require that the full range of tissues masticated be tested. Synthesizing data on ingestive and masticatory behaviors, the number of chewing cycles associated with a given food, and food mechanical properties, should inform the broader question of which foods and feeding behaviors are most influential on the mandibular loading environment.
Highly oxygenated organic molecules (HOMs) contribute
substantially to the formation and growth of atmospheric aerosol particles,
which affect air quality, human health and Earth's climate. HOMs are ...formed
by rapid, gas-phase autoxidation of volatile organic compounds (VOCs) such
as α-pinene, the most abundant monoterpene in the atmosphere. Due to
their abundance and low volatility, HOMs can play an important role in
new-particle formation (NPF) and the early growth of atmospheric aerosols,
even without any further assistance of other low-volatility compounds such
as sulfuric acid. Both the autoxidation reaction forming HOMs and their
NPF rates are expected to be strongly dependent on
temperature. However, experimental data on both effects are limited.
Dedicated experiments were performed at the CLOUD (Cosmics Leaving OUtdoor
Droplets) chamber at CERN to address this question. In this study, we show
that a decrease in temperature (from +25 to −50 ∘C) results in
a reduced HOM yield and reduced oxidation state of the products, whereas the
NPF rates (J1.7 nm) increase substantially.
Measurements with two different chemical ionization mass spectrometers
(using nitrate and protonated water as reagent ion, respectively) provide
the molecular composition of the gaseous oxidation products, and a
two-dimensional volatility basis set (2D VBS) model provides their volatility
distribution. The HOM yield decreases with temperature from 6.2 % at 25 ∘C to 0.7 % at −50 ∘C. However, there is a strong
reduction of the saturation vapor pressure of each oxidation state as the
temperature is reduced. Overall, the reduction in volatility with
temperature leads to an increase in the nucleation rates by up to 3
orders of magnitude at −50 ∘C compared with 25 ∘C. In
addition, the enhancement of the nucleation rates by ions decreases with
decreasing temperature, since the neutral molecular clusters have increased
stability against evaporation. The resulting data quantify how the interplay
between the temperature-dependent oxidation pathways and the associated
vapor pressures affect biogenic NPF at the molecular
level. Our measurements, therefore, improve our understanding of pure
biogenic NPF for a wide range of tropospheric
temperatures and precursor concentrations.
Disease staging, whereby the spatial extent and load of brain pathology are used to estimate the severity of Alzheimer disease (AD), is pivotal to the gold-standard neuropathological diagnosis of AD. ...Current in vivo diagnostic frameworks for AD are based on abnormal concentrations of amyloid-β and tau in the cerebrospinal fluid or on PET scans, and breakthroughs in molecular imaging have opened up the possibility of in vivo staging of AD. Focusing on the key principles of disease staging shared across several areas of medicine, this Review highlights the potential for in vivo staging of AD to transform our understanding of preclinical AD, refine enrolment criteria for trials of disease-modifying therapies and aid clinical decision-making in the era of anti-amyloid therapeutics. We provide a state-of-the-art review of recent biomarker-based AD staging systems and highlight their contributions to the understanding of the natural history of AD. Furthermore, we outline hypothetical frameworks to stage AD severity using more accessible fluid biomarkers. In addition, by applying amyloid PET-based staging to recently published anti-amyloid therapeutic trials, we highlight how biomarker-based disease staging frameworks could illustrate the numerous pathological changes that have already taken place in individuals with mildly symptomatic AD. Finally, we discuss challenges related to the validation and standardization of disease staging and provide a forward-looking perspective on potential clinical applications.
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