Apes communicate about absent and displaced objects: methodology matters

Displaced reference is the ability to refer to an item that has been moved (displaced) in space and/or time, and has been called one of the true hallmarks of referential communication. Several studies suggest that nonhuman primates have this capability, but a recent experiment concluded that in a specific situation (absent entities) human infants display displaced reference but chimpanzees do not. Here we show that chimpanzees and bonobos of diverse rearing histories are capable of displaced reference to absent and displaced objects. It is likely that some of the conflicting findings from animal cognition studies are due to relatively minor methodological differences, but are compounded by interpretation errors. Comparative studies are of great importance in elucidating the evolution of human cognition, however, greater care must be taken with methodology and interpretation for these studies to accurately reflect species differences

Triggering social interactions:chimpanzees respond to imitation by a humanoid robot and request responses from it

Even the most rudimentary social cues may evoke affiliative responses in humans and promote socialcommunication and cohesion. The present work tested whether such cues of an agent may also promotecommunicative interactions in a nonhuman primate species, by examining interaction-promoting behavioursin chimpanzees. Here, chimpanzees were tested during interactions with an interactive humanoid robot, whichshowed simple bodily movements and sent out calls. The results revealed that chimpanzees exhibited twotypes of interaction-promoting behaviours during relaxed or playful contexts. First, the chimpanzees showedprolonged active interest when they were imitated by the robot. Second, the subjects requested ‘social’responses from the robot, i.e. by showing play invitations and offering toys or other objects. This study thusprovides evidence that even rudimentary cues of a robotic agent may promote social interactions inchimpanzees, like in humans. Such simple and frequent social interactions most likely provided a foundationfor sophisticated forms of affiliative communication to emerge

Handedness for Unimanual Grasping in 564 Great Apes: The Effect on Grip Morphology and a Comparison with Hand Use for a Bimanual Coordinated Task

A number of factors have been proposed to influence within and between species variation in handedness in non-human primates. In the initial study, we assessed the influence of grip morphology on hand use for simple reaching in a sample of 564 great apes including 49 orangutans Pongo pygmaeus, 66 gorillas Gorilla gorilla, 354 chimpanzees Pan troglodytes and 95 bonobos Pan paniscus. Overall, we found a significant right hand bias for reaching. We also found a significant effect of the grip morphology of hand use. Grasping with the thumb and index finger was more prevalent in the right compared to left hand in all four species. There was no significant sex effect on the patterns of handedness. In a subsample of apes, we also compared consistency in hand use for simple reaching with previously published data on a task that measures handedness for bimanual actions. We found that the ratio of subjects with consistent right compared to left hand use was more prevalent in bonobos, chimpanzees and gorillas but not orangutans. However, for all species, the proportion of subjects with inconsistent hand preferences between the tasks was relatively high suggesting some measures may be more sensitive in assessing handedness than others

Field-Grown Transgenic Switchgrass (Panicum virgatum L.) with Altered Lignin Does Not Affect Soil Chemistry, Microbiology, and Carbon Storage Potential

Cell wall recalcitrance poses a major challenge on cellulosic biofuel production from feedstocks such as switchgrass (Panicum virgatum L.). As lignin is a known contributor of recalcitrance, transgenic switchgrass plants with altered lignin have been produced by downregulation of caffeic acid O-methyltransferase (COMT). Field trials of COMT-downregulated plants previously demonstrated improved ethanol conversion with no adverse agronomic effects. However, the rhizosphere impacts of altering lignin in plants are unknown. We hypothesized that changing plant lignin composition may affect residue degradation in soils, ultimately altering soil processes. The objective of this study was to evaluate effects of two independent lines of COMT-downregulated switchgrass plants on soils in terms of chemistry, microbiology, and carbon cycling when grown in the field. Over the first two years of establishment, we observed no significant differences between transgenic and control plants in terms of soil pH or the total concentrations of 19 elements. An analysis of soil bacterial communities via high-throughput 16S rRNA gene amplicon sequencing revealed no effects of transgenic plants on bacterial diversity, richness, or community composition. We also did not observe a change in the capacity for soil carbon storage: There was no significant effect on soil respiration or soil organic matter. After five years of establishment, δ13C of plant roots, leaves, and soils was measured and an isotopic mixing model used to estimate that 11.2 to 14.5% of soil carbon originated from switchgrass. Switchgrass-contributed carbon was not significantly different between transgenic and control plants. Overall, our results indicate that over the short term (two and five years), lignin modification in switchgrass through manipulation of COMT expression does not have an adverse effect on soils in terms of total elemental composition, bacterial community structure and diversity, and capacity for carbon storage

T-Cell Infiltration and Adaptive Treg Resistance in Response to Androgen Deprivation With or Without Vaccination in Localized Prostate Cancer

Purpose: Previous studies suggest that androgen deprivation therapy (ADT) promotes antitumor immunity in prostate cancer. Whether a vaccine-based approach can augment this effect remains unknown. Experimental Design: Therefore, we conducted a neoadjuvant, randomized study to quantify the immunologic effects of a granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic cellular vaccine in combination with low-dose cyclophosphamide (Cy/GVAX) followed by degarelix versus degarelix alone in patients with high-risk localized prostate adenocarcinoma who were planned for radical prostatectomy. Results: Both Cy/GVAX plus degarelix and degarelix alone led to significant increases in intratumoral CD8+ T cell infiltration and PD-L1 expression as compared to a cohort of untreated, matched controls. However, the CD8+ T cell infiltrate was accompanied by a proportional increase in regulatory T cells (Treg), suggesting that adaptive Treg resistance may dampen the immunogenicity of ADT. Although Cy/GVAX followed by degarelix was associated with a modest improvement in time-to-PSA progression and time-to-next treatment as well as an increase in PD-L1, there was no difference in the CD8 T-cell infiltrate as compared to degarelix alone. Gene expression profiling demonstrated that CHIT1, a macrophage marker, was differentially upregulated with Cy/GVAX plus degarelix compared to degarelix alone. Conclusions: Our results highlight that ADT with or without Cy/GVAX induces a complex immune response within the prostate tumor microenvironment. These data have important implications for combining ADT with immunotherapy. In particular, our finding that ADT increases both CD8+ T cells and Tregs, supports the development of regimens combining ADT with Treg-depleting agents in the treatment of prostate cancer

Management of pediatric renal trauma: Results from the American Association for Surgery and Trauma Multi-Institutional Pediatric Acute Renal Trauma Study

BackgroundPediatric renal trauma is rare and lacks sufficient population-specific data to generate evidence-based management guidelines. A nonoperative approach is preferred and has been shown to be safe. However, bleeding risk assessment and management of collecting system injury are not well understood. We introduce the Multi-institutional Pediatric Acute Renal Trauma Study (Mi-PARTS), a retrospective cohort study designed to address these questions. This article describes the demographics and contemporary management of pediatric renal trauma at Level I trauma centers in the United States.MethodsRetrospective data were collected at 13 participating Level I trauma centers on pediatric patients presenting with renal trauma between 2010 and 2019. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Descriptive statistics were used to report on demographics, acute management, and outcomes.ResultsIn total, 1,216 cases were included in this study. Of all patients, 67.2% were male, and 93.8% had a blunt injury mechanism. In addition, 29.3% had isolated renal injuries, and 65.6% were high-grade (American Association for the Surgery of Trauma Grades III-V) injuries. The mean Injury Severity Score was 20.5. Most patients were managed nonoperatively (86.4%), and 3.9% had an open surgical intervention, including 2.7% having nephrectomy. Angioembolization was performed in 0.9%. Collecting system intervention was performed in 7.9%. Overall mortality was 3.3% and was only observed in patients with multiple injuries. The rate of avoidable transfer was 28.2%.ConclusionThe management and outcomes of pediatric renal trauma lack data to inform evidence-based guidelines. Nonoperative management of bleeding following renal injury is a well-established practice. Intervention for renal trauma is rare. Our findings reinforce differences from the adult population and highlights opportunities for further investigation. With data made available through Mi-PARTS, we aimed to answer pediatric specific questions, including a pediatric-specific bleeding risk nomogram, and better understanding indications for interventions for collecting system injuries.Level of evidencePrognostic and Epidemiological; Level IV

Cortical Representation of Lateralized Grasping in Chimpanzees (Pan troglodytes): A Combined MRI and PET Study

Functional imaging studies in humans have localized the motor-hand region to a neuroanatomical landmark call the KNOB within the precentral gyrus. It has also been reported that the KNOB is larger in the hemisphere contralateral to an individual's preferred hand, and therefore may represent the neural substrate for handedness. The KNOB has also been neuronatomically described in chimpanzees and other great apes and is similarly associated with handedness. However, whether the chimpanzee KNOB represents the hand region is unclear from the extant literature. Here, we used PET to quantify neural metabolic activity in chimpanzees when engaged in unilateral reach-and-grasping responses and found significantly lateralized activation of the KNOB region in the hemisphere contralateral to the hand used by the chimpanzees. We subsequently constructed a probabilistic map of the KNOB region in chimpanzees in order to assess the overlap in consistency in the anatomical landmarks of the KNOB with the functional maps generated from the PET analysis. We found significant overlap in the anatomical and functional voxels comprising the KNOB region, suggesting that the KNOB does correspond to the hand region in chimpanzees. Lastly, from the probabilistic maps, we compared right- and left-handed chimpanzees on lateralization in grey and white matter within the KNOB region and found that asymmetries in white matter of the KNOB region were larger in the hemisphere contralateral to the preferred hand. These results suggest that neuroanatomical asymmetries in the KNOB likely reflect changes in connectivity in primary motor cortex that are experience dependent in chimpanzees and possibly humans

A Mouse Model of the Human Fragile X Syndrome I304N Mutation

The mental retardation, autistic features, and behavioral abnormalities characteristic of the Fragile X mental retardation syndrome result from the loss of function of the RNA–binding protein FMRP. The disease is usually caused by a triplet repeat expansion in the 5′UTR of the FMR1 gene. This leads to loss of function through transcriptional gene silencing, pointing to a key function for FMRP, but precluding genetic identification of critical activities within the protein. Moreover, antisense transcripts (FMR4, ASFMR1) in the same locus have been reported to be silenced by the repeat expansion. Missense mutations offer one means of confirming a central role for FMRP in the disease, but to date, only a single such patient has been described. This patient harbors an isoleucine to asparagine mutation (I304N) in the second FMRP KH-type RNA–binding domain, however, this single case report was complicated because the patient harbored a superimposed familial liver disease. To address these issues, we have generated a new Fragile X Syndrome mouse model in which the endogenous Fmr1 gene harbors the I304N mutation. These mice phenocopy the symptoms of Fragile X Syndrome in the existing Fmr1–null mouse, as assessed by testicular size, behavioral phenotyping, and electrophysiological assays of synaptic plasticity. I304N FMRP retains some functions, but has specifically lost RNA binding and polyribosome association; moreover, levels of the mutant protein are markedly reduced in the brain specifically at a time when synapses are forming postnatally. These data suggest that loss of FMRP function, particularly in KH2-mediated RNA binding and in synaptic plasticity, play critical roles in pathogenesis of the Fragile X Syndrome and establish a new model for studying the disorder

Mechanisms of viral entry: sneaking in the front door

Recent developments in methods to study virus internalisation are providing clearer insights into mechanisms used by viruses to enter host cells. The use of dominant negative constructs, specific inhibitory drugs and RNAi to selectively prevent entry through particular pathways has provided evidence for the clathrin-mediated entry of hepatitis C virus (HCV) as well as the caveolar entry of Simian Virus 40. Moreover, the ability to image and track fluorescent-labelled virus particles in real-time has begun to challenge the classical plasma membrane entry mechanisms described for poliovirus and human immunodeficiency virus. This review will cover both well-documented entry mechanisms as well as more recent discoveries in the entry pathways of enveloped and non-enveloped viruses. This will include viruses which enter the cytosol directly at the plasma membrane and those which enter via endocytosis and traversal of internal membrane barrier(s). Recent developments in imaging and inhibition of entry pathways have provided insights into the ill-defined entry mechanism of HCV, bringing it to the forefront of viral entry research. Finally, as high-affinity receptors often define viral internalisation pathways, and tropism in vivo, host membrane proteins to which viral particles specifically bind will be discussed throughout