Body mass estimates of phytosaurs (Archosauria: Parasuchidae) from the Petrified Forest Formation (Chinle Group: Revueltian : early-mid Norian) based on skull and limb bone measurements

Phytosaurs were the largest and most common semi-aquatic predators of the Late Triassic. Although their skulls are relatively common in the fossil record, articulated, or even associated skeletons are extremely rare, so it has always been difficult to gauge just how large (mass or length) an individual phytosaur may have been. Body mass in particular is an important physiological variable, often used for the scaling of organs, biomass determination, biomechanics, and locomotion. We take advantage of phytosaurs’ general similarity to extant crocodilians to attempt to reconstruct body mass and length based on measurements of the skulls and limbs of phytosaurs from the Upper Triassic Snyder and Canjilon quarries in north-central New Mexico. These quarries, in the Painted Desert Member of the Petrified Forest Formation (Revueltian: early-mid Norian) preserve catastrophic death assemblages that appear to well-represent discrete populations of phytosaurs. We also utilize a snout-vent measurement based on an articulated skeleton from the Canjilon quarry to compare the accuracy of different equations based on discrete limb elements. Body mass estimates for Snyder quarry phytosaurs range between 25 and 500 kg, with most specimens yielding estimates of approximately 200-350 kg. The Canjilon quarry sample encompasses fewer juveniles and more robust adults, including one individual that may have weighed as much as 535 kg. From equations based on nine extant crocodilian genera, these Revueltian phytosaurs appear to have approached 4.5 m total body length for a ~ 400 kg phytosaur. The prevalence of subadult to adult phytosaurs in both quarries based on body mass estimates corroborates qualitative estimates of the population structure based on skull sizes alone, thereby reinforcing the hypothesis that both quarries are catastrophic assemblages

Structural Analysis of an Avr4 Effector Ortholog Offers Insight into Chitin Binding and Recognition by the Cf-4 Receptor

Chitin is a key component of fungal cell walls and a potent inducer of innate immune responses. Consequently, fungi may secrete chitin-binding lectins, such as the Cf-Avr4 effector protein from the tomato pathogen Cladosporium fulvum, to shield chitin from host-derived chitinases during infection. Homologs of Cf-Avr4 are found throughout Dothideomycetes, and despite their modest primary sequence identity, many are perceived by the cognate tomato immune receptor Cf-4. Here, we determined the x-ray crystal structure of Pf-Avr4 from the tomato pathogen Pseudocercospora fuligena, thus providing a three-dimensional model of an Avr4 effector protein. In addition, we explored structural, biochemical, and functional aspects of Pf-Avr4 and Cf-Avr4 to further define the biology of core effector proteins and outline a conceptual framework for their pleiotropic recognition by single immune receptors. We show that Cf-Avr4 and Pf-Avr4 share functional specificity in binding (GlcNAc)(6) and in providing protection against plant- and microbial-derived chitinases, suggesting a broader role beyond deregulation of host immunity. Furthermore, structure-guided site-directed mutagenesis indicated that residues in Pf-Avr4 important for binding chitin do not directly influence recognition by Cf-4 and further suggested that the property of recognition is structurally separated or does not fully overlap with the virulence function of the effector

Predicting sepsis severity at first clinical presentation:The role of endotypes and mechanistic signatures

BACKGROUND: Inter-individual variability during sepsis limits appropriate triage of patients. Identifying, at first clinical presentation, gene expression signatures that predict subsequent severity will allow clinicians to identify the most at-risk groups of patients and enable appropriate antibiotic use. METHODS: Blood RNA-Seq and clinical data were collected from 348 patients in four emergency rooms (ER) and one intensive-care-unit (ICU), and 44 healthy controls. Gene expression profiles were analyzed using machine learning and data mining to identify clinically relevant gene signatures reflecting disease severity, organ dysfunction, mortality, and specific endotypes/mechanisms. FINDINGS: Gene expression signatures were obtained that predicted severity/organ dysfunction and mortality in both ER and ICU patients with accuracy/AUC of 77–80%. Network analysis revealed these signatures formed a coherent biological program, with specific but overlapping mechanisms/pathways. Given the heterogeneity of sepsis, we asked if patients could be assorted into discrete groups with distinct mechanisms (endotypes) and varying severity. Patients with early sepsis could be stratified into five distinct and novel mechanistic endotypes, named Neutrophilic-Suppressive/NPS, Inflammatory/INF, Innate-Host-Defense/IHD, Interferon/IFN, and Adaptive/ADA, each based on ∼200 unique gene expression differences, and distinct pathways/mechanisms (e.g., IL6/STAT3 in NPS). Endotypes had varying overall severity with two severe (NPS/INF) and one relatively benign (ADA) groupings, consistent with reanalysis of previous endotype studies. A 40 gene-classification tool (accuracy=96%) and several gene-pairs (accuracy=89–97%) accurately predicted endotype status in both ER and ICU validation cohorts. INTERPRETATION: The severity and endotype signatures indicate that distinct immune signatures precede the onset of severe sepsis and lethality, providing a method to triage early sepsis patients

Huntingtin Interacting Proteins Are Genetic Modifiers of Neurodegeneration

Huntington's disease (HD) is a fatal neurodegenerative condition caused by expansion of the polyglutamine tract in the huntingtin (Htt) protein. Neuronal toxicity in HD is thought to be, at least in part, a consequence of protein interactions involving mutant Htt. We therefore hypothesized that genetic modifiers of HD neurodegeneration should be enriched among Htt protein interactors. To test this idea, we identified a comprehensive set of Htt interactors using two complementary approaches: high-throughput yeast two-hybrid screening and affinity pull down followed by mass spectrometry. This effort led to the identification of 234 high-confidence Htt-associated proteins, 104 of which were found with the yeast method and 130 with the pull downs. We then tested an arbitrary set of 60 genes encoding interacting proteins for their ability to behave as genetic modifiers of neurodegeneration in a Drosophila model of HD. This high-content validation assay showed that 27 of 60 orthologs tested were high-confidence genetic modifiers, as modification was observed with more than one allele. The 45% hit rate for genetic modifiers seen among the interactors is an order of magnitude higher than the 1%–4% typically observed in unbiased genetic screens. Genetic modifiers were similarly represented among proteins discovered using yeast two-hybrid and pull-down/mass spectrometry methods, supporting the notion that these complementary technologies are equally useful in identifying biologically relevant proteins. Interacting proteins confirmed as modifiers of the neurodegeneration phenotype represent a diverse array of biological functions, including synaptic transmission, cytoskeletal organization, signal transduction, and transcription. Among the modifiers were 17 loss-of-function suppressors of neurodegeneration, which can be considered potential targets for therapeutic intervention. Finally, we show that seven interacting proteins from among 11 tested were able to co-immunoprecipitate with full-length Htt from mouse brain. These studies demonstrate that high-throughput screening for protein interactions combined with genetic validation in a model organism is a powerful approach for identifying novel candidate modifiers of polyglutamine toxicity

Phantasia - the psychological significance of lifelong visual imagery vividness extremes

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordVisual imagery typically enables us to see absent items in the mind’s eye. It plays a role in memory, day-dreaming and creativity. Since coining the terms aphantasia and hyperphantasia to describe the absence and abundance of visual imagery, we have been contacted by many thousands of people with extreme imagery abilities. Questionnaire data from 2000 participants with aphantasia and 200 with hyperphantasia indicate that aphantasia is associated with scientific and mathematical occupations, whereas hyperphantasia is associated with ‘creative’ professions. Participants with aphantasia report an elevated rate of difficulty with face recognition and autobiographical memory, whereas participants with hyperphantasia report an elevated rate of synaesthesia. Around half those with aphantasia describe an absence of wakeful imagery in all sense modalities, while a majority dream visually. Aphantasia appears to run within families more often than would be expected by chance. Aphantasia and hyperphantasia appear to be widespread but neglected features of human experience with informative psychological associations.Arts and Humanities Research Council (AHRC

Structured bimanual actions and hand transfers reveal population-level right-handedness in captive gorillas

There is a common prevailing perception that humans possess a species-unique population-level right-hand bias that has evolutionary links with language. New theories suggest that an early evolutionary division of cognitive function gave rise to a left-hemisphere bias for behaviours underpinned by structured sequences of actions. However, studies of great ape handedness have generated inconsistent results and considerable debate. Additionally, the literature places a heavy focus on chimpanzees, revealing a paucity of handedness findings from other great ape species, and thus limiting the empirical evidence with which we can evaluate evolutionary theory. We observed handedness during spontaneous naturalistic bimanual actions in a captive, biological group of 13 western lowland gorillas, Gorilla gorilla gorilla. Our results demonstrated a significant group-level right-handed bias for bimanual actions as well as for a novel measure of handedness: hand transfer. The two measures revealed similar patterns of handedness, such that a right-hand bias for the majority of individuals was found across both measures. Our findings suggest that human population-level right-handedness is a behavioural trait linked with left-hemisphere dominance for the processing of structured sequences of actions, and was inherited by a common ancestor of both humans and apes

Neuroimaging the consciousness of self: Review, and conceptual-methodological framework

We review neuroimaging research investigating self-referential processing (SRP), that is, how we respond to stimuli that reference ourselves, prefaced by a lexical-thematic analysis of words indicative of “self-feelings”. We consider SRP as occurring verbally (V-SRP) and non-verbally (NV-SRP), both in the controlled, “top-down” form of introspective and interoceptive tasks, respectively, as well as in the “bottom-up” spontaneous or automatic form of “mind wandering” and “body wandering” that occurs during resting state. Our review leads us to outline a conceptual and methodological framework for future SRP research that we briefly apply toward understanding certain psychological and neurological disorders symptomatically associated with abnormal SRP. Our discussion is partly guided by William James’ original writings on the consciousness of self