1,420 research outputs found
Impact of Carnivory on Human Development and Evolution Revealed by a New Unifying Model of Weaning in Mammals
Our large brain, long life span and high fertility are key elements of human evolutionary success and are often thought to have evolved in interplay with tool use, carnivory and hunting. However, the specific impact of carnivory on human evolution, life history and development remains controversial. Here we show in quantitative terms that dietary profile is a key factor influencing time to weaning across a wide taxonomic range of mammals, including humans. In a model encompassing a total of 67 species and genera from 12 mammalian orders, adult brain mass and two dichotomous variables reflecting species differences regarding limb biomechanics and dietary profile, accounted for 75.5%, 10.3% and 3.4% of variance in time to weaning, respectively, together capturing 89.2% of total variance. Crucially, carnivory predicted the time point of early weaning in humans with remarkable precision, yielding a prediction error of less than 5% with a sample of forty-six human natural fertility societies as reference. Hence, carnivory appears to provide both a necessary and sufficient explanation as to why humans wean so much earlier than the great apes. While early weaning is regarded as essentially differentiating the genus Homo from the great apes, its timing seems to be determined by the same limited set of factors in humans as in mammals in general, despite some 90 million years of evolution. Our analysis emphasizes the high degree of similarity of relative time scales in mammalian development and life history across 67 genera from 12 mammalian orders and shows that the impact of carnivory on time to weaning in humans is quantifiable, and critical. Since early weaning yields shorter interbirth intervals and higher rates of reproduction, with profound effects on population dynamics, our findings highlight the emergence of carnivory as a process fundamentally determining human evolution
ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer
\ua9 The Author(s) 2024.Immune checkpoint blockade has yet to produce robust anti-cancer responses for prostate cancer. Sialyltransferases have been shown across several solid tumours, including breast, melanoma, colorectal and prostate to promote immune suppression by synthesising sialoglycans, which act as ligands for Siglec receptors. We report that ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) levels negatively correlate with androgen signalling in prostate tumours. We demonstrate that ST3Gal1 plays an important role in modulating tumour immune evasion through the synthesises of sialoglycans with the capacity to engage the Siglec-7 and Siglec-9 immunoreceptors preventing immune clearance of cancer cells. Here, we provide evidence of the expression of Siglec-7/9 ligands and their respective immunoreceptors in prostate tumours. These interactions can be modulated by enzalutamide and may maintain immune suppression in enzalutamide treated tumours. We conclude that the activity of ST3Gal1 is critical to prostate cancer anti-tumour immunity and provide rationale for the use of glyco-immune checkpoint targeting therapies in advanced prostate cancer
A New Mechanistic Scenario for the Origin and Evolution of Vertebrate Cartilage
The appearance of cellular cartilage was a defining event in vertebrate evolution because it made possible the physical expansion of the vertebrate “new head”. Despite its central role in vertebrate evolution, the origin of cellular cartilage has been difficult to understand. This is largely due to a lack of informative evolutionary intermediates linking vertebrate cellular cartilage to the acellular cartilage of invertebrate chordates. The basal jawless vertebrate, lamprey, has long been considered key to understanding the evolution of vertebrate cartilage. However, histological analyses of the lamprey head skeleton suggest it is composed of modern cellular cartilage and a putatively unrelated connective tissue called mucocartilage, with no obvious transitional tissue. Here we take a molecular approach to better understand the evolutionary relationships between lamprey cellular cartilage, gnathostome cellular cartilage, and lamprey mucocartilage. We find that despite overt histological similarity, lamprey and gnathostome cellular cartilage utilize divergent gene regulatory networks (GRNs). While the gnathostome cellular cartilage GRN broadly incorporates Runx, Barx, and Alx transcription factors, lamprey cellular cartilage does not express Runx or Barx, and only deploys Alx genes in certain regions. Furthermore, we find that lamprey mucocartilage, despite its distinctive mesenchymal morphology, deploys every component of the gnathostome cartilage GRN, albeit in different domains. Based on these findings, and previous work, we propose a stepwise model for the evolution of vertebrate cellular cartilage in which the appearance of a generic neural crest-derived skeletal tissue was followed by a phase of skeletal tissue diversification in early agnathans. In the gnathostome lineage, a single type of rigid cellular cartilage became dominant, replacing other skeletal tissues and evolving via gene cooption to become the definitive cellular cartilage of modern jawed vertebrates
Measurement of B(t->Wb)/B(t->Wq) at the Collider Detector at Fermilab
We present a measurement of the ratio of top-quark branching fractions R= B(t
-> Wb)/B(t -> Wq), where q can be a b, s or a d quark, using lepton-plus-jets
and dilepton data sets with integrated luminosity of ~162 pb^{-1} collected
with the Collider Detector at Fermilab during Run II of the Tevatron. The
measurement is derived from the relative numbers of t-tbar events with
different multiplicity of identified secondary vertices. We set a lower limit
of R > 0.61 at 95% confidence level.Comment: 7 pages, 2 figures, published in Physical Review Letters; changes
made to be consistent with published versio
Search for ZZ and ZW Production in ppbar Collisions at sqrt(s) = 1.96 TeV
We present a search for ZZ and ZW vector boson pair production in ppbar
collisions at sqrt(s) = 1.96 TeV using the leptonic decay channels ZZ --> ll nu
nu, ZZ --> l l l' l' and ZW --> l l l' nu. In a data sample corresponding to an
integrated luminosity of 194 pb-1 collected with the Collider Detector at
Fermilab, 3 candidate events are found with an expected background of 1.0 +/-
0.2 events. We set a 95% confidence level upper limit of 15.2 pb on the cross
section for ZZ plus ZW production, compared to the standard model prediction of
5.0 +/- 0.4 pb.Comment: 7 pages, 2 figures. This version is accepted for publication by Phys.
Rev. D Rapid Communication
Measurement of the Cross Section for Prompt Diphoton Production in p-pbar Collisions at sqrt(s) = 1.96 TeV
We report a measurement of the rate of prompt diphoton production in
collisions at using a data sample of 207
pb collected with the upgraded Collider Detector at Fermilab (CDF II).
The background from non-prompt sources is determined using a statistical method
based on differences in the electromagnetic showers. The cross section is
measured as a function of the diphoton mass, the transverse momentum of the
diphoton system, and the azimuthal angle between the two photons and is found
to be consistent with perturbative QCD predictions.Comment: 7 pages, 3 figures,revtex4. Version accepted by PRL, but with cross
section tables i
External validation of a COPD prediction model using population-based primary care data: a nested case-control study
Emerging models for predicting risk of chronic obstructive pulmonary disease (COPD) require external validation in order to assess their clinical value. We validated a previous model for predicting new onset COPD in a different database. We randomly drew 38,597 case-control pairs (total N = 77,194) of individuals aged ≥35 years and matched for sex, age, and general practice from the United Kingdom Clinical Practice Research Datalink database. We assessed accuracy of the model to discriminate between COPD cases and non-cases by calculating area under the receiver operator characteristic (ROC(AUC)) for the prediction scores. Analogous to the development model, ever smoking (OR 6.70; 95%CI 6.41–6.99), prior asthma (OR 6.43; 95%CI 5.85–7.07), and higher socioeconomic deprivation (OR 2.90; 95%CI 2.72–3.09 for highest vs. lowest quintile) increased the risk of COPD. The validated prediction scores ranged from 0–5.71 (ROC(AUC) 0.66; 95%CI 0.65–0.66) for males and 0–5.95 (ROC(AUC) 0.71; 95%CI 0.70–0.71) for females. We have confirmed that smoking, prior asthma, and socioeconomic deprivation are key risk factors for new onset COPD. Our model seems externally valid at identifying patients at risk of developing COPD. An impact assessment now needs to be undertaken to assess whether this prediction model can be applied in clinical care settings
Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay
We reconstruct the rare decays , , and in a data sample
corresponding to collected in collisions at
by the CDF II detector at the Fermilab Tevatron
Collider. Using and decays we report the branching ratios. In addition, we report
the measurement of the differential branching ratio and the muon
forward-backward asymmetry in the and decay modes, and the
longitudinal polarization in the decay mode with respect to the squared
dimuon mass. These are consistent with the theoretical prediction from the
standard model, and most recent determinations from other experiments and of
comparable accuracy. We also report the first observation of the {\mathcal{B}}(B^0_s \to
\phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}27 \pm 6B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let
Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons
We report measurements of the resonance properties of Lambda_c(2595)+ and
Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as
Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+
pi+/- final states. These measurements are performed using data corresponding
to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV,
collected with the CDF II detector at the Fermilab Tevatron. Exploiting the
largest available charmed baryon sample, we measure masses and decay widths
with uncertainties comparable to the world averages for Sigma_c states, and
significantly smaller uncertainties than the world averages for excited
Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17
pages, 15 figure
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