Site fidelity and behavioral plasticity regulate an ungulate’s response to extreme disturbance

With rapid global change, the frequency and severity of extreme disturbance events are increasing worldwide. The ability of animal populations to survive these stochastic events depends on how individual animals respond to their altered environments, yet our understanding of the immediate and short‐term behavioral responses of animals to acute disturbances remains poor. We focused on animal behavioral responses to the environmental disturbance created by megafire. Specifically, we explored the effects of the 2018 Mendocino Complex Fire in northern California, USA, on the behavior and body condition of black‐tailed deer (Odocoileus hemionus columbianus). We predicted that deer would be displaced by the disturbance or experience high mortality post‐fire if they stayed in the burn area. We used data from GPS collars on 18 individual deer to quantify patterns of home range use, movement, and habitat selection before and after the fire. We assessed changes in body condition using images from a camera trap grid. The fire burned through half of the study area, facilitating a comparison between deer in burned and unburned areas. Despite a dramatic reduction in vegetation in burned areas, deer showed high site fidelity to pre‐fire home ranges, returning within hours of the fire. However, mean home range size doubled after the fire and corresponded to increased daily activity in a severely resource‐depleted environment. Within their home ranges, deer also selected strongly for patches of surviving vegetation and woodland habitat, as these areas provided forage and cover in an otherwise desolate landscape. Deer body condition significantly decreased after the fire, likely as a result of a reduction in forage within their home ranges, but all collared deer survived for the duration of the study. Understanding the ways in which large mammals respond to disturbances such as wildfire is increasingly important as the extent and severity of such events increases across the world. While many animals are adapted to disturbance regimes, species that exhibit high site fidelity or otherwise fixed behavioral strategies may struggle to cope with increased climate instability and associated extreme disturbance events.     

Age-Dependent Cell Trafficking Defects in Draining Lymph Nodes Impair Adaptive Immunity and Control of West Nile Virus Infection

Impaired immune responses in the elderly lead to reduced vaccine efficacy and increased susceptibility to viral infections. Although several groups have documented age-dependent defects in adaptive immune priming, the deficits that occur prior to antigen encounter remain largely unexplored. Herein, we identify novel mechanisms for compromised adaptive immunity that occurs with aging in the context of infection with West Nile virus (WNV), an encephalitic flavivirus that preferentially causes disease in the elderly. An impaired IgM and IgG response and enhanced vulnerability to WNV infection during aging was linked to delayed germinal center formation in the draining lymph node (DLN). Adoptive transfer studies and two-photon intravital microscopy revealed a decreased trafficking capacity of donor naïve CD4⁺ T cells from old mice, which manifested as impaired T cell diapedesis at high endothelial venules and reduced cell motility within DLN prior to antigen encounter. Furthermore, leukocyte accumulation in the DLN within the first few days of WNV infection or antigen-adjuvant administration was diminished more generally in old mice and associated with a second aging-related defect in local cytokine and chemokine production. Thus, age-dependent cell-intrinsic and environmental defects in the DLN result in delayed immune cell recruitment and antigen recognition. These deficits compromise priming of early adaptive immune responses and likely contribute to the susceptibility of old animals to acute WNV infection.     

Reorienting the Fab Domains of Trastuzumab Results in Potent HER2 Activators

The structure of the Fab region of antibodies is critical to their function. By introducing single cysteine substitutions into various positions of the heavy and light chains of the Fab region of trastuzumab, a potent antagonist of HER2, and using thiol chemistry to link the different Fabs together, we produced a variety of monospecific F(ab′)₂-like molecules with activities spanning from activation to inhibition of breast tumor cell growth. These isomers (or bis-Fabs) of trastuzumab, with varying relative spatial arrangements between the Fv-regions, were able to either promote or inhibit cell-signaling activities through the PI3K/AKT and MAPK pathways. A quantitative phosphorylation mapping of HER2 indicated that the agonistic isomers produced a distinct phosphorylation pattern associated with activation. This study suggests that antibody geometric isomers, found both in nature and during synthetic antibody development, can have profoundly different biological activities independent of their affinities for their target molecules.     

Phylogenetic analysis of coadaptation in behavior, diet, and body size in the African antelope

Several authors have suggested that African antelope (familyBovidae) exemplify coadaptation of ecological, behavioral,and morphological traits. We tested four hypotheses relatedto the ecology and behavior of 75 species of African antelopeusing both conventional statistical techniques and techniques that account for the nonindependence of species by consideringtheir phylogenetic relationships. Specifically, we tested thehypotheses that (1) dietary selectivity is correlated negativelywith body mass, (2) dietary selectivity is correlated negativelywith group size, (3) gregarious species either flee or counterattackwhen approached by predators, but solitary and pair-livingspecies seek cover to hide, and (4) body mass and group sizeare correlated positively. Each of these hypotheses was examinedfor the global data set (family Bovidae) and, when possible,within the two antelope subfamilies (Antilopinae and Bovinae)and within 7 of the 10 antelope tribes. The results of ourconventional and phylogenetically corrected analyses supportedthe hypotheses that group and body size vary predictably with feeding style and that antipredator behavior varies with groupsize. The hypothesis that body mass and group size are correlatedpositively was supported by conventional statistics, but thesetwo traits were only weakly related using a phylogeneticallycorrected analysis. Moreover, qualitative and quantitativecomparisons within each of the eight major African antelope tribes generally gave little support for the four hypothesestested. Thus, although our analyses at the subfamily levelprovided results that were consistent with prior hypotheses,our analyses at the level of tribes were equivocal. We discussseveral possible explanations for these differences.     

Receptor-mediated adenylyl cyclase activation through XLalpha(s), the extra-large variant of the stimulatory G protein alpha-subunit

XLalpha(s), the large variant of the stimulatory G protein alpha subunit (Gsalpha), is derived from GNAS1 through the use of an alternative first exon and promoter. Gs(alpha) and XLalpha(s) have distinct amino-terminal domains, but are identical over the carboxyl-terminal portion encoded by exons 2-13. XLalpha(s) can mimic some functions of Gs(alpha), including betagamma interaction and adenylyl cyclase stimulation. However, previous attempts to demonstrate coupling of XLalpha(s) to typically Gs-coupled receptors have not been successful. We now report the generation of murine cell lines that carry homozygous disruption of Gnas exon 2, and are therefore null for endogenous XLalpha(s) and Gs(alpha) (Gnas(E2-/E2-)). Gnas(E2-/E2-) cells transfected with plasmids encoding XLalpha(s) and different heptahelical receptors, including the beta2-adrenergic receptor and receptors for PTH, TSH, and CRF, showed agonist-mediated cAMP accumulation that was indistinguishable from that observed with cells transiently coexpressing Gs(alpha) and these receptors. Our findings thus indicate that XLalpha(s) is capable of functionally coupling to receptors that normally act via Gs(alpha).     

Local force cues for strength and stability in a distributed robotic construction system

Construction of spatially extended, self-supporting structures requires a consideration of structural stability throughout the building sequence. For collective construction systems, where independent agents act with variable order and timing under decentralized control, ensuring stability is a particularly pronounced challenge. Previous research in this area has largely neglected considering stability during the building process. Physical forces present throughout a structure may be usable as a cue to inform agent actions as well as an indirect communication mechanism (stigmergy) to coordinate their behavior, as adding material leads to redistribution of forces which then informs the addition of further material. Here we consider in simulation a system of decentralized climbing robots capable of traversing and extending a two-dimensional truss structure, and explore the use of feedback based on force sensing as a way for the swarm to anticipate and prevent structural failures. We consider a scenario in which robots are tasked with building an unsupported cantilever across a gap, as for a bridge, where the goal is for the swarm to build any stable spanning structure rather than to construct a specific predetermined blueprint. We show that access to local force measurements enables robots to build cantilevers that span significantly farther than those built by robots without access to such information. This improvement is achieved by taking measures to maintain both strength and stability, where strength is ensured by paying attention to forces during locomotion to prevent joints from breaking, and stability is maintained by looking at how loads transfer to the ground to ensure against toppling. We show that swarms that take both kinds of forces into account have improved building performance, in both structured settings with flat ground and unpredictable environments with rough terrain.     

137 DNA nanostructure serum stability: greater than the sum of their parts

DNA cages hold tremendous potential to encapsulate and selectively release therapeutic drugs, and can provide useful tools to probe the size and shape dependence of nucleic acid delivery (McLaughlin & Sleiman, H. F., 2011). These structures have been shown to site-specifically present ligands, small molecule drugs, or antisense/siRNA motifs, in order to increase their therapeutic efficiency (Li & Fan, C. 2012). One of the major barriers towards their in vivo applications is the susceptibility of their strands towards nuclease degradation. A number of chemical strategies have been used to block nuclease digestion of oligonucleotides and improve potency, such as the use of a phosphorothioate backbone, 2´-O-methyl, locked nucleic acids, and short hybrid gapmers. However, the synthesis of these oligonucleotides is often complicated and expensive, driving the need for simple modifications to enhance serum stability and address in vivo biodistribution. We show here a simple method to significantly enhance the nuclease stability of DNA strands, through introduction of commercially available, single-endmodifications (Conway & Sleiman 2013). We use these oligonucleotides to construct DNA cages in a single step and in quantitative yields. Even in single-stranded form, these cages stabilize their component strands towards nucleases, with mean lifetimes as long as 62?h in 10 % (v/v) fetal bovine serum (FBS). We examine the effect of other DNA-end modifications on nuclease susceptibility. Finally, we show the ligation of these single-stranded cages into topologically interesting catenane ‘necklaces,’ with mean lifetimes in serum of ～200?h.