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It is generally thought that behavioral flexibility, the ability to change behavior when circumstances change, plays an important role in the ability of species to rapidly expand their geographic range. Great-tailed grackles (Quiscalus mexicanus) are a social, polygamous species that is rapidly expanding its geographic range by settling in new areas and habitats. They are behaviorally flexible and highly associated with human-modified environments, eating a variety of human foods in addition to foraging on insects and on the ground for other natural food items. They offer an opportunity to assess the role of behavior change over the course of their expansion. We compared behavior in wild-caught grackles from two populations across their range (an older population in the middle of the northern expansion front: Tempe, Arizona, and a more recent population on the northern edge of the expansion front: Woodland, California) to investigate whether certain behaviors (flexibility, innovativeness, exploration, and persistence) have higher averages and variances in the newer or older population. We found that grackles in the edge population had a higher flexibility variance (measured by reversal learning) and a higher persistence average (they participated in a larger proportion of trials), and that there were no population differences in average levels of flexibility, innovativeness (number of loci solved on a multiaccess box), or exploration (latency to approach a novel environment). Our results elucidated that individuals differentially expressing a particular behavior in an edge population could facilitate the rapid geographic range expansion of great-tailed grackles, and we found no support for the importance of several traits that were hypothesized to be involved in such an expansion. Our findings highlight the value of population studies and of breaking down cognitive concepts into direct measures of individual abilities to better understand how species might adapt to novel circumstances.

Behavioral flexibility, the ability to adapt behavior to new circumstances, is thought to play an important role in a species’ ability to successfully adapt to new environments and expand its geographic range. However, flexibility is rarely directly tested in a way that would allow us to determine how flexibility works to predict a species’ ability to adapt their behavior to new environments. We use great-tailed grackles (Quiscalus mexicanus; a bird species) as a model to investigate this question because they have recently rapidly expanded their range into North America. We attempted to manipulate grackle flexibility using shaded (light and dark gray) tube reversal learning to determine whether flexibility is generalizable across contexts (multi-access box), and what learning strategies grackles employ. We found that flexibility was manipulable: birds in the manipulated group took fewer trials to pass criterion with increasing reversal number, and they reversed a shade preference in fewer trials by the end of their serial reversals compared to control birds who had only one reversal. Birds that passed their last reversal faster were also more flexible (faster to switch between loci) and innovative (solved more loci) on a multi-access box. All grackles in the manipulated reversal learning group used one learning strategy (epsilon-decreasing) in all reversals, and none used a particular exploration or exploitation strategy earlier or later in their serial reversals. Understanding how flexibility causally relates to other traits will allow researchers to develop robust theory about what flexibility is and when to invoke it as a primary driver in a given context, such as a rapid geographic range expansion.

UNLABELLED: This study characterized and compared the fecal and oral microbiota from women with early-stage breast cancer (BC), women with ductal carcinoma in situ (DCIS), and healthy women. Fecal and oral samples were collected from newly diagnosed patients prior to any therapy and characterized using 16S rRNA sequencing. Measures of gut microbial alpha diversity were significantly lower in the BC vs healthy cohort. Beta diversity differed significantly between the BC or DCIS and healthy groups, and several differentially abundant taxa were identified. Clustering (non-negative matrix factorization) of the gut microbiota identified five bacterial guilds dominated by Prevotella, Enterobacteriaceae, Akkermansia, Clostridiales, or Bacteroides. The Bacteroides and Enterobacteriaceae guilds were significantly more abundant in the BC cohort compared to healthy controls, whereas the Clostridiales guild was more abundant in the healthy group. Finally, prediction of functional pathways identified 23 pathways that differed between the BC and healthy gut microbiota including lipopolysaccharide biosynthesis, glycan biosynthesis and metabolism, lipid metabolism, and sphingolipid metabolism. In contrast to the gut microbiomes, there were no significant differences in alpha or beta diversity in the oral microbiomes, and very few differentially abundant taxa were observed. Non-negative matrix factorization analysis of the oral microbiota samples identified seven guilds dominated by Veillonella, Prevotella, Gemellaceae, Haemophilus, Neisseria, Propionibacterium, and Streptococcus; however, none of these guilds were differentially associated with the different cohorts. Our results suggest that alterations in the gut microbiota may provide the basis for interventions targeting the gut microbiome to improve treatment outcomes and long-term prognosis. IMPORTANCE: Emerging evidence suggests that the gut microbiota may play a role in breast cancer. Few studies have evaluated both the gut and oral microbiomes in women with breast cancer (BC), and none have characterized these microbiomes in women with ductal carcinoma in situ (DCIS). We surveyed the gut and oral microbiomes from women with BC or DCIS and healthy women and identified compositional and functional features of the gut microbiota that differed between these cohorts. In contrast, very few differential features were identified in the oral microbiota. Understanding the role of gut bacteria in BC and DCIS may open up new opportunities for the development of novel markers for early detection (or markers of susceptibility) as well as new strategies for prevention and/or treatment.

Dose optimization of sirolimus may further improve outcomes in allogeneic hematopoietic cell transplant (HCT) patients receiving post-transplantation cyclophosphamide (PTCy) to prevent graft-versus-host disease (GVHD). Sirolimus exposure-response association studies in HCT patients (i.e., the association of trough concentration with clinical outcomes) have been conflicting. Sirolimus has important effects on T-cells, including conventional (Tcons) and regulatory T-cells (Tregs), both of which have been implicated in the mechanisms by which PTCy prevents GVHD, but there is an absence of validated biomarkers of sirolimus effects on these cell subsets. Considering the paucity of existing biomarkers and the complexities of the immune system, we conducted a literature review to inform a quantitative systems pharmacology (QSP) model of GVHD. The published literature presented multiple challenges. The sirolimus pharmacokinetic models insufficiently describe sirolimus distribution to relevant physiological compartments. Despite multiple publications describing sirolimus effects on Tcons and Tregs in preclinical and human ex vivo models, consistent parameters relating sirolimus concentrations to circulating Tcons and Tregs could not be found. Each aspect presents a challenge in building a QSP model of sirolimus and its temporal effects on T-cell subsets and GVHD prevention. To optimize GVHD prevention regimens, phase I studies and systematic studies of immunosuppressant concentration-effect association are needed for QSP modeling.

We study thermal production of dark matter (DM) in a realization of the minimal models of Bonnefoy et al. [Phys. Rev. Lett. 131, 221802 (2023)PRLTAO0031-900710.1103/PhysRevLett.131.221802], where parity is used to solve the strong CP problem by transforming the entire Standard Model (SM) into a mirror copy. Although the mirror electron e′ is a good DM candidate, its viability is mired by the presence of the mirror up quark u′, whose abundance is intimately related to the e′ abundance and must be suppressed. This can be achieved through a sequential freeze-in mechanism, where mirror photons are first produced from SM gluons, and then the mirror photons produce e′. After computing the details of this double freeze-in, we discuss the allowed parameter space of the model, which lies at the threshold of experimental observations. We find that this origin of e′ DM requires a low reheating temperature after inflation and is consistent with the baryon asymmetry arising from leptogenesis, providing mirror neutrinos have a significant degeneracy. Finally, we show that this e′ DM is not compatible with Higgs parity, the simplest scheme with exact parity, unless SM parameters deviate significantly from their central values or the minimal model is extended.