The mechanical response of fire ant rafts

Fire ants (Solenopsis invicta) cohesively aggregate via the formation of voluntary ant-to-ant attachments when under confinement or exposed to water. Once formed, these aggregations act as viscoelastic solids due to dynamic bond exchange between neighboring ants as demonstrated by rate-dependent mechanical response of 3D aggregations, confined in rheometers. We here investigate the mechanical response of 2D, planar ant rafts roughly as they form in nature. Specifically, we load rafts under uniaxial tension to failure, as well as to 50% strain for two cycles with various recovery times between. We do so while measuring raft reaction force (to estimate network-scale stress), as well as the networks' instantaneous velocity fields and topological damage responses to elucidate the ant-scale origins of global mechanics. The rafts display brittle-like behavior even at slow strain rates (relative to the unloaded bond detachment rate) for which Transient Network Theory predicts steady-state creep. This provides evidence that loaded ant-to-ant bonds undergo mechanosensitive bond stabilization or act as \say{catch bonds}. This is further supported by the coalescence of voids that nucleate due to biaxial stress conditions and merge due to bond dissociation. The characteristic timescales of void coalescence due to chain dissociation provide evidence that the local detachment of stretched bonds is predominantly strain- (as opposed to bond lifetime-) dependent, even at slow strain rates, implying that bond detachment rates diminish significantly under stretch. Significantly, when the voids are closed by restoring the rafts to unstressed conditions, mechanical recovery occurs, confirming the presence of concentration-dependent bond association that - combined with force-diminished dissociation - could further bolster network cohesion under certain stress states

FoxP2 isoforms delineate spatiotemporal transcriptional networks for vocal learning in the zebra finch.

Human speech is one of the few examples of vocal learning among mammals yet ~half of avian species exhibit this ability. Its neurogenetic basis is largely unknown beyond a shared requirement for FoxP2 in both humans and zebra finches. We manipulated FoxP2 isoforms in Area X, a song-specific region of the avian striatopallidum analogous to human anterior striatum, during a critical period for song development. We delineate, for the first time, unique contributions of each isoform to vocal learning. Weighted gene coexpression network analysis of RNA-seq data revealed gene modules correlated to singing, learning, or vocal variability. Coexpression related to singing was found in juvenile and adult Area X whereas coexpression correlated to learning was unique to juveniles. The confluence of learning and singing coexpression in juvenile Area X may underscore molecular processes that drive vocal learning in young zebra finches and, by analogy, humans

BCAA catabolism in brown fat controls energy homeostasis through SLC25A44.

Branched-chain amino acid (BCAA; valine, leucine and isoleucine) supplementation is often beneficial to energy expenditure; however, increased circulating levels of BCAA are linked to obesity and diabetes. The mechanisms of this paradox remain unclear. Here we report that, on cold exposure, brown adipose tissue (BAT) actively utilizes BCAA in the mitochondria for thermogenesis and promotes systemic BCAA clearance in mice and humans. In turn, a BAT-specific defect in BCAA catabolism attenuates systemic BCAA clearance, BAT fuel oxidation and thermogenesis, leading to diet-induced obesity and glucose intolerance. Mechanistically, active BCAA catabolism in BAT is mediated by SLC25A44, which transports BCAAs into mitochondria. Our results suggest that BAT serves as a key metabolic filter that controls BCAA clearance via SLC25A44, thereby contributing to the improvement of metabolic health

A measure of individual role in collective dynamics

Identifying key players in collective dynamics remains a challenge in several research fields, from the efficient dissemination of ideas to drug target discovery in biomedical problems. The difficulty lies at several levels: how to single out the role of individual elements in such intermingled systems, or which is the best way to quantify their importance. Centrality measures describe a node's importance by its position in a network. The key issue obviated is that the contribution of a node to the collective behavior is not uniquely determined by the structure of the system but it is a result of the interplay between dynamics and network structure. We show that dynamical influence measures explicitly how strongly a node's dynamical state affects collective behavior. For critical spreading, dynamical influence targets nodes according to their spreading capabilities. For diffusive processes it quantifies how efficiently real systems may be controlled by manipulating a single node.Comment: accepted for publication in Scientific Report

Making Connections - Envisioning Springfield\u27s North End

This work explores a service learning strategy in the context of the senior Urban Design Studio taught in the Department of Landscape Architecture and Regional Planning at the University of Massachusetts Amherst. The primary goal of this project is to stimulate a conversation in the neighborhoods of the North End, to develop green design strategies, to improve services and businesses for residents and the employees of local businesses, and to foster cultural engagement and interaction in the North End that will enhance the vibrancy, resilience, and quality of life of this urban community. Making connections - Envisioning Springfield\u27s North End proposes improved connectivity in a physical, cultural, and social sense will be key to attaining these goals and to engaging and synergizing individuals and community groups in the North End - residents, businesses, schools, churches, employers, and employees. Six sustainable learning and planning principles have emerged from this studio: 1. Input and interaction – Visioning workshops connect campus and community 2. Community-building art - Expression of place and people 3. Healthy living - Urban agriculture and education 4. Urban greenways – Abandoned railways and urban rivers and streams 5. Green infrastructure - Green streets as networks and structural framework 6. Sustainable urban form – Mixed use and pedestrian friendly neighborhood

No association between a candidate TCF7L2 variant and risk of breast or ovarian cancer

<p>Abstract</p> <p>Background</p> <p>TCF7L2 is a transcription factor involved in Wnt/β-catenin signaling which has a variant known to be associated with risk of Type 2 diabetes and, in some studies, with risk of certain cancers, including familial breast cancer. No studies of ovarian cancer have been reported to date.</p> <p>Methods</p> <p>Two clinic-based case-control studies at the Mayo Clinic were assessed including 798 breast cancer cases, 843 breast cancer controls, 391 ovarian cancer cases, and 458 ovarian cancer controls. Genotyping at <it>TCF7L2 </it>rs12255372 used a 5' endonuclease assay, and statistical analysis used logistic regression among participants as a whole and among <it>a priori</it>-defined subsets.</p> <p>Results</p> <p>No associations with risk of breast or ovarian cancer were observed (ordinal model, p = 0.62 and p = 0.75, respectively). In addition, no associations were observed among sub-groups defined by age, BMI, family history, stage, grade, histology, or tumor behavior.</p> <p>Conclusion</p> <p>Although the biology of the Wnt/β-catenin signaling pathway and prior association between rs12255372 and numerous phenotypes warranted examination of this <it>TCF7L2 </it>SNP, no compelling evidence for association with breast or ovarian cancer was observed.</p

Short-term treatment with multi-drug regimens combining BRAF/MEK-targeted therapy and immunotherapy results in durable responses in Braf-mutated melanoma

Targeted and immunotherapy regimens have revolutionized the treatment of advanced melanoma patients. Despite this, only a subset of patients respond durably. Recently, combination strategies of BRAF/MEK inhibitors with immune checkpoint inhibitor monotherapy (α-CTLA-4 or α-PD-1) have increased the rate of durable responses. Based on evidence from our group and others, these therapies appear synergistic, but at the cost of significant toxicity. We know from other treatment paradigms (e.g. hematologic malignancies) that combination strategies with multi-drug regimens (\u3e4 drugs) are associated with more durable disease control. To better understand the mechanism of these improved outcomes, and to identify and prioritize new strategies for testing, we studied several multi-drug regimens combining BRAF/MEK targeted therapy and immunotherapy combinations in a Braf-mutant murine melanoma model (BrafV600E/Pten−/−). Short-term treatment with α-PD-1 and α-CTLA-4 monotherapies were relatively ineffective, while treatment with α-OX40 demonstrated some efficacy [17% of mice with no evidence of disease, (NED), at 60-days]. Outcomes were improved in the combined α-OX40/α-PD-1 group (42% NED). Short-term treatment with quadruplet therapy of immunotherapy doublets in combination with targeted therapy [dabrafenib and trametinib (DT)] was associated with excellent tumor control, with 100% of mice having NED after combined DT/α-CTLA-4/α-PD-1 or DT/α-OX40/α-PD-1. Notably, tumors from mice in these groups demonstrated a high proportion of effector memory T cells, and immunologic memory was maintained with tumor re-challenge. Together, these data provide important evidence regarding the potential utility of multi-drug therapy in treating advanced melanoma and suggest these models can be used to guide and prioritize combinatorial treatment strategies

Hyperleptinemia Is Required for the Development of Leptin Resistance

Leptin regulates body weight by signaling to the brain the availability of energy stored as fat. This negative feedback loop becomes disrupted in most obese individuals, resulting in a state known as leptin resistance. The physiological causes of leptin resistance remain poorly understood. Here we test the hypothesis that hyperleptinemia is required for the development of leptin resistance in diet-induced obese mice. We show that mice whose plasma leptin has been clamped to lean levels develop obesity in response to a high-fat diet, and the magnitude of this obesity is indistinguishable from wild-type controls. Yet these obese animals with constant low levels of plasma leptin remain highly sensitive to exogenous leptin even after long-term exposure to a high fat diet. This shows that dietary fats alone are insufficient to block the response to leptin. The data also suggest that hyperleptinemia itself can contribute to leptin resistance by downregulating cellular response to leptin as has been shown for other hormones

The Atacama Cosmology Telescope: Cosmology from cross-correlations of unWISE galaxies and ACT DR6 CMB lensing

We present tomographic measurements of structure growth using cross-correlations of Atacama Cosmology Telescope (ACT) DR6 and Planck CMB lensing maps with the unWISE Blue and Green galaxy samples, which span the redshift ranges $0.2 \lesssim z \lesssim 1.1$ and $0.3 \lesssim z \lesssim 1.8$, respectively. We improve on prior unWISE cross-correlations not just by making use of the new, high-precision ACT DR6 lensing maps, but also by including additional spectroscopic data for redshift calibration and by analysing our measurements with a more flexible theoretical model. An extensive suite of systematic and null tests within a blind analysis framework ensures that our results are robust. We determine the amplitude of matter fluctuations at low redshifts ($z\simeq 0.2-1.6$), finding $S_8 \equiv \sigma_8 (\Omega_m / 0.3)^{0.5} = 0.813 \pm 0.021$ using the ACT cross-correlation alone and $S_8 = 0.810 \pm 0.015$ with a combination of Planck and ACT cross-correlations; these measurements are fully consistent with the predictions from primary CMB measurements assuming standard structure growth. The addition of Baryon Acoustic Oscillation data breaks the degeneracy between $\sigma_8$ and $\Omega_m$, allowing us to measure $\sigma_8 = 0.813 \pm 0.020$ from the cross-correlation of unWISE with ACT and $\sigma_8 = 0.813\pm 0.015$ from the combination of cross-correlations with ACT and Planck. These results also agree with the expectations from primary CMB extrapolations in $\Lambda$CDM cosmology; the consistency of $\sigma_8$ derived from our two redshift samples at $z \sim 0.6$ and $1.1$ provides a further check of our cosmological model. Our results suggest that structure formation on linear scales is well described by $\Lambda$CDM even down to low redshifts $z\lesssim 1$.Comment: 73 pages (incl. 30 pages of appendices), 50 figures, 16 tables, to be submitted to ApJ. Watch G. S. Farren and A. Krolewski discuss the analysis and results under https://cosmologytalks.com/2023/09/11/act-unwis