Center for Glial Neuronal Interactions

The Salton Sea is a drying salt lake in an arid region with high aerosol particulate-matter concentrations. This region is plagued by a high incidence of asthma, attributed in part to the aerosols surrounding the Sea. But the connection between the Sea and asthma may be more than simple calculations of dust concentrations. While dusts might contain toxic substances that impact the lungs of residents, the complex dynamics related to the environmental degradation of the Salton Sea may be generating additional toxins relevant to public health, such as microcystins produced by algal blooms. This collection of pollutants may be driving inflammatory responses in the lungs of residents through multiple mechanisms. As such, examination of the full range of potential environmental triggers of lung inflammation promises to yield a better understanding of key mechanisms driving the high incidence of asthma in local residents. Our discussion provides a perspective aiming to re-frame the issue in the context of the historical theory of “miasma” and the linkages between environmental change and health impacts.

The onset of parental care in female mammals is associated with plasticity in neural processing of infant-related sensory stimuli, which enhances mothers’ ability to detect and care for their offspring; however, little is known about sensory plasticity in fathers. We tested the hypothesis that parenthood alters neural responses to olfactory and auditory stimuli from infants in male and female California mice (Peromyscus californicus), a biparental rodent. Virgins and new parents of both sexes were exposed to a combination of a chemosensory stimulus (pup-scented or unscented cotton [control]) and an auditory stimulus (pup vocalizations or white noise [control]). Brains were collected one hour later and stained immunohistochemically for Fos, an index of neural activity. We quantified Fos in the main olfactory bulbs (MOB), a region essential to receiving olfactory information, and medial preoptic area (MPOA), a region critical for parental behavior. We predicted that Fos in MOB and MPOA would be greater in parents than virgins, especially after exposure to pup stimuli. We found that in females, MPOA and MOB Fos did not differ between virgins and mothers or across treatment groups. In contrast, fathers had lower expression of Fos in MOB but higher expression in MPOA, compared to virgin males. Moreover, Fos in MPOA was higher in males exposed to pup vocalizations and pup scent compared to those exposed exclusively to pup vocalizations. Fos in MPOA was also higher in males exposed to scent or both scent and vocalization stimuli compared to males exposed to control stimuli. These findings suggest that the onset of parenthood alters activity in the MOB and MPOA, especially in response to pup vocalizations and scents, in males but not females in this biparental rodent.

In many biparental mammalian species, such as California mice (Peromyscus cali- fornicus), new fathers exhibit affiliative behavior toward unfamiliar infants, whereas reproductively naïve males show highly variable behavioral responses to infants. The sources of this variation are unknown. We investigated the effects of acute stress on pup-directed behavior in reproductively naïve male California mice. Each mouse underwent three 10-minute tests with an unfamiliar pup at 48-hour intervals. Males in the stressed group (N=22) were stressed using subcutane- ous oil injections, a common experimental stressor used in rodents, immediate- ly before each of the first two tests. The controls (N=22) were left undisturbed to avoid any experimentally induced stress. Compared to controls, stressed mice spent significantly less time performing paternal behavior in tests 1 and 2, while only marginal differences were seen in test 3. In tests 2 and 3, signifi- cantly fewer stressed mice interacted with the pup than controls. These findings suggest that acute stress experienced by reproductively naïve males might con- tribute to both short-term and long-term differences in pup-directed behavior.

Reassortment between different influenza strains occurs when they co-infect the same host cell. The emergence of a reassortant virus depends on both its intrinsic fitness and extrinsic factors, including preexisting humoral immunity. The generation of pandemic strains, such as H2N2 and H3N2, and zoonotic influenza A viruses, such as H5N6, H5N8, and H7N9, in birds is suggested to be the result of extensive selection by preexisting antibodies. To further explore the role of humoral immunity in reassortment, we generated two divergent fluorescent protein-expressing viruses and used strain-specific and cross-reactive monoclonal antibodies (mAbs) to assess the impact of cross-immunity on reassortment. Our results indicate that all mAbs altered the genotypic diversity and significantly reduced the release of progeny virions in co-infected cells both in vitro and in vivo. Moreover, antibody transfer studies in mice revealed protection from challenge with divergent pathogenicity profiles. Notably, selection driven by a strain-specific mAb depended on its neutralizing specificity, whereas the selection driven by broadly reactive mAbs was independent of neutralization specificity. Our findings demonstrate that preexisting neutralizing antibodies shape reassortment and that strain-specific neutralizing antibodies promote antigenic shift during co-infection, which is not the case for broadly cross-reactive antibodies that recognize influenza viruses from different subtypes.

A zoonotic Babesia species previously referred to as Babesia sp. MO1 is formally described and named here as Babesia hegotelforum sp. nov. This taxon is distinct from Babesia divergens based on genome-wide sequence divergence, phylogenetic placement, host associations, and clinical presentation. The parasite infects erythrocytes of humans, and eastern cottontail rabbits (Sylvilagus floridanus), and is transmitted by Ixodes dentatus. The holotype consists of a Giemsa-stained thin blood smear and cryopreserved infected erythrocytes from the cloned isolate BML-Bh-B12 at ≤10 passages in continuous in vitro culture. Paratype material includes five additional clones (BML-Bh-H1, BML-Bh-F12, BML-Bh-H6, BML-Bh-A3, and BML-Bh-F1) derived from BEI Resources strain NR-50441, along with the original mixed isolate NR-50441. This species description meets the requirements of the International Code of Zoological Nomenclature and establishes Babesia hegotelforum sp. nov. as a distinct species of clinical and epidemiological significance in North America.

We build upon Haueis and Colaço's account in two ways. First, we argue that the backgrounding of metabolism was a pragmatic response to a data granularity problem faced by traditional cognitive modelers. Then, we suggest that equivalence demonstrations offer a promising pathway for incrementally introducing metabolic considerations into extant modeling practice.

Bumble bees are essential pollinators that have an annual eusocial lifestyle where new cohorts of queens establish colonies each season. The early stages of colony establishment are critical for colony success and are heavily impacted by how readily queens activate their ovaries and initiate egg laying at the start of the season. Understanding the social and nesting factors that influence queen reproduction may provide key insights into early colony establishment. Here, we examine how social conditions and nest cavity size affect the onset of egg laying in early nesting Bombus impatiens queens. In the first experiment, queens were assigned to a social condition where they were placed into nesting boxes that either completely restricted contact with nestmates (and were smaller in size) or allowed direct physical contact and then housed either alone or with nestmates (males or workers). We found that contact with either workers or males accelerated egg laying in queens relative to being housed alone. Unexpectedly, queens housed in the restricted cages, regardless of whether alone or with nestmates, also initiated egg laying earlier. This led us to a second experiment, where we examined ovarian activation and hemolymph juvenile hormone (JH-III) concentrations in early queens housed in different nesting cavity sizes. Here, we found that smaller nest cavity sizes lead to a greater degree of ovarian activation in gynes (young, unmated queens), but juvenile hormone concentrations did not differ. Our findings demonstrate that both social conditions and nest cavity size influence reproductive timing in queens in early-stage bumble bee colonies.

Host-pathogen interactions are shaped by cellular restriction factors that direct antiviral defenses. We built the first ovine genome-wide CRISPR knockout library in sheep testis (OA3.Ts) cells, targeting all protein-coding genes. Using this platform, we identified PEX11B, a peroxisomal membrane regulatory protein, as a strong restriction factor against orf virus (ORFV) infection. Removing PEX11B increased viral susceptibility and triggered severe cytopathic effects with membrane fusion and syncytia formation. Mechanistic studies showed that PEX11B knockout harmed peroxisomal integrity and disrupted lipid metabolism. This led to greater plasma membrane fluidity, creating a proviral environment that allowed more viral entry and replication. These results reveal a new antiviral function for PEX11B in blocking viral infection and underscore the importance of peroxisomal regulation in host-virus interactions.

Neural crest (NC) cells are multipotent cells unique to vertebrates that arise early in development, at the edge of the neural plate, and subsequently undergo an epithelial to mesenchymal transition, migrate throughout the body, and differentiate into many different derivatives, contributing to the formation of many organs and systems. NC induction research from multiple modeling organisms has identified critical roles for a few signaling pathways, including Wnt, BMP, FGF, Notch/ Delta, Indian Hedgehog, and Endothelin signaling (Prasad et al., 2019). Given the limitations of human embryo studies, pluripotent stem cell models of human NC formation have provided a resourceful alternative (Lee et al., 2007). Intriguingly, while TGFβ inhibition had not been identified as a signaling requirement for NC formation in any in vivo model organism, several pluripotent stem cell (PSC) models of human NC induction rely on TGFβ inhibition (Chambers et al., 2009). To address this issue, we evaluate the role of TGFβ in NC formation using our human (hNC) model that depends on WNT signaling and does not require TGFβ inhibition (Leung et al., 2016, Gomez et al., 2019). We report that under our model, TGFβ signaling is required, and that moderate levels of TGFβ and pSMAD2 levels are necessary for optimal NC formation (with negative effects seen upon strong activation or inhibition). Moreover, we demonstrate that PSC cultured in mTeSR1 immediately prior to hNC induction instead required TGFβ modulation in addition to WNT signaling activation to render hNC. Using the chick embryo as an in vivo vertebrate model, we further provide evidence of expression and requirement of relevant TGFβ signaling components during NC formation. This study identifies an important role for TGFβ signaling in early NC development, opening the door for novel players as effectors mediating the multiple signals integrated during early neural crest development.