A late-surviving basal theropod dinosaur from the latest Triassic of North America

The oldest theropod dinosaurs are known from the Carnian of Argentina and Brazil. However, the evolutionary diversification of this group after its initial radiation but prior to the Triassic-Jurassic boundary is still poorly understood because of a sparse fossil record near that boundary. Here, we report on a new basal theropod, Daemonosaurus chauliodus gen. et sp. nov., from the latest Triassic 'siltstone member' of the Chinle Formation of the Coelophysis Quarry at Ghost Ranch, New Mexico. Based on a comprehensive phylogenetic analysis, Daemonosaurus is more closely related to coeval neotheropods (e.g. Coelophysis bauri) than to Herrerasauridae and Eoraptor. The skeletal structure of Daemonosaurus and the recently discovered Tawa bridge a morphological gap between Eoraptor and Herrerasauridae on one hand and neotheropods on the other, providing additional support for the theropod affinities of both Eoraptor and Herrerasauridae and demonstrating that lineages from the initial radiation of Dinosauria persisted until the end of the Triassic. Various features of the skull of Daemonosaurus, including the procumbent dentary and premaxillary teeth and greatly enlarged premaxillary and anterior maxillary teeth, clearly set this taxon apart from coeval neotheropods and demonstrate unexpected disparity in cranial shape among theropod dinosaurs just prior to the end of the Triassic.     

Primary and secondary restraints of human and ovine knees for simulated in vivo gait kinematics

Knee soft tissue structures are frequently injured, leading to the development of osteoarthritis even with treatment. Understanding how these structures contribute to knee function during activities of daily living (ADLs) is crucial in creating more effective treatments. This study was designed to determine the role of different knee structures during a simulated ADL in both human knees and ovine stifle joints. A six degree-of-freedom robot was used to reproduce each species’ in vivo gait while measuring three-dimensional joint forces and torques. Using a semi-randomized selective cutting method, we determined the primary and secondary structures contributing to the forces and torques along and about each anatomical axis. In both species, the bony interaction, ACL, and medial meniscus provided most of the force contributions during stance, whereas the ovine MCL, human bone, and ACLs of both species were the key contributors during swing. This study contributes to our overarching goal of establishing functional tissue engineering parameters for knee structures by further validating biomechanical similarities between the ovine model and the human to provide a platform for measuring biomechanics during an in vivo ADL. These parameters will be used to develop more effective treatments for knee injuries to reduce or eliminate the incidence of osteoarthritis.     

Global State Measures of the Dentate Gyrus Gene Expression System Predict Antidepressant-Sensitive Behaviors

Background

Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are the most common form of medication treatment for major depression. However, approximately 50% of depressed patients fail to achieve an effective treatment response. Understanding how gene expression systems respond to treatments may be critical for understanding antidepressant resistance.

Methods

We take a novel approach to this problem by demonstrating that the gene expression system of the dentate gyrus responds to fluoxetine (FLX), a commonly used antidepressant medication, in a stereotyped-manner involving changes in the expression levels of thousands of genes. The aggregate behavior of this large-scale systemic response was quantified with principal components analysis (PCA) yielding a single quantitative measure of the global gene expression system state.

Results

Quantitative measures of system state were highly correlated with variability in levels of antidepressant-sensitive behaviors in a mouse model of depression treated with fluoxetine. Analysis of dorsal and ventral dentate samples in the same mice indicated that system state co-varied across these regions despite their reported functional differences. Aggregate measures of gene expression system state were very robust and remained unchanged when different microarray data processing algorithms were used and even when completely different sets of gene expression levels were used for their calculation.

Conclusions

System state measures provide a robust method to quantify and relate global gene expression system state variability to behavior and treatment. State variability also suggests that the diversity of reported changes in gene expression levels in response to treatments such as fluoxetine may represent different perspectives on unified but noisy global gene expression system state level responses. Studying regulation of gene expression systems at the state level may be useful in guiding new approaches to augmentation of traditional antidepressant treatments.     

Single-Molecule Kinetics Reveal Cation-Promoted DNA Duplex Formation Through Ordering of Single-Stranded Helices

In this work, the kinetics of short, fully complementary oligonucleotides are investigated at the single-molecule level. Constructs 6–9 bp in length exhibit single exponential kinetics over 2 orders of magnitude time for both forward (k_on, association) and reverse (k_off, dissociation) processes. Bimolecular rate constants for association are weakly sensitive to the number of basepairs in the duplex, with a 2.5-fold increase between 9 bp (k′_on = 2.1(1) × 10⁶ M⁻¹ s⁻¹) and 6 bp (k′_on = 5.0(1) × 10⁶ M⁻¹ s⁻¹) sequences. In sharp contrast, however, dissociation rate constants prove to be exponentially sensitive to sequence length, varying by nearly 600-fold over the same 9 bp (k_off = 0.024 s⁻¹) to 6 bp (k_off = 14 s⁻¹) range. The 8 bp sequence is explored in more detail, and the NaCl dependence of k_on and k_off is measured. Interestingly, k_onincreases by >40-fold (k_on = 0.10(1) s⁻¹ to 4.0(4) s⁻¹ between [NaCl] = 25 mM and 1 M), whereas in contrast, k_offdecreases by fourfold (0.72(3) s⁻¹ to 0.17(7) s⁻¹) over the same range of conditions. Thus, the equilibrium constant (K_eq) increases by ≈160, largely due to changes in the association rate, k_on. Finally, temperature-dependent measurements reveal that increased [NaCl] reduces the overall exothermicity (ΔΔH° > 0) of duplex formation, albeit by an amount smaller than the reduction in entropic penalty (−TΔΔS° < 0). This reduced entropic cost is attributed to a cation-facilitated preordering of the two single-stranded species, which lowers the association free-energy barrier and in turn accelerates the rate of duplex formation.     

Osteology of the Middle Triassic pseudosuchian archosaur Arizonasaurus babbitti

Arizonasaurus babbitti is rediagnosed from a well-preserved partial skeleton from the early Middle Triassic Moenkopi Formation of northern Arizona. The skull, excluding the braincase, is described and compared to other “rauisuchians” and basal archosaurs. Two possible autapomorphies include a deep fossa hidden from lateral and medial views on the posteroventral edge of the ascending process of the maxilla and a tongue (pubic peduncle of the ilium) and groove (proximal portion of the pubis) articulation between the pubis and the ilium.

The postcrania is described in detail. Tall neural spines form a sail that is similar to those of other basal archosaurs with unknown affinities (Ctenosauriscus, Lotosaurus, Bromsgroveia, “Hypselorhachis”). Additional characters in the pelvic girdle in Arizonasaurus unite this taxon with Ctenosauriscus, Lotosaurus, Bromsgroveia, and Hypselorhachus to form a group, the ctenosauriscids. Pelvic characters of the ctenosauriscids are also found in Poposaurus and “Chatterjeea”, suggesting that ctenosauriscids are closely related. A possibly monophyletic group containing Arizonasaurus, other ctenosauriscids, Poposaurus, Sillosuchus, and “Chatterjeea” the exclusions of most other rauisuchians is proposed based on a new understanding of pseudosuchian characters.     

Formatting antibody fragments to mediate specific therapeutic functions

Monoclonal antibodies are increasingly being used as therapeutic agents in a wide range of indications, including oncology, inflammation and infectious disease. In most cases the basis of the therapeutic function is the high degree of specificity and affinity the antibody-based drug has for its target antigen. However, the mechanism of action (MOA), the way the drug takes advantage of this specificity to mediate a therapeutic effect, varies considerably from drug to drug. Three basic potential categories of MOAs exist: antagonists, agonists and specific delivery mechanisms to target an active function to a particular cell type. The latter functions include selective cell killing, based on Fc-mediated events, recruitment of effector cells, and drug or radioisotope delivery. The majority of these mechanisms are not necessarily optimally mediated by an IgG structure; clearly, in the case of antibody-dependent cellular cytotoxicity or complement-mediated lysis, Fc is required. However, Fab fragments (the fragment comprising one antigen-binding arm of the Y-shaped IgG molecule) can be formatted to mediate most mechanisms and have the advantage that valency and half-life can be controlled to simplify the drug and address only the mechanism required. Moreover, Fab fragments can be produced in microbial expression systems which address manufacturing issues such as scale of supply and cost of goods.     

Contractile behavior of the forelimb digital flexors during steady-state locomotion in horses (Equus caballus): an initial test of muscle architectural hypotheses about in vivo function

The forelimb digital flexors of the horse display remarkable diversity in muscle architecture despite each muscle-tendon unit having a similar mechanical advantage across the fetlock joint. We focus on two distinct muscles of the digital flexor system: short compartment deep digital flexor (DDF(sc)) and the superficial digital flexor (SDF). The objectives were to investigate force-length behavior and work performance of these two muscles in vivo during locomotion, and to determine how muscle architecture contributes to in vivo function in this system. We directly recorded muscle force (via tendon strain gauges) and muscle fascicle length (via sonomicrometry crystals) as horses walked (1.7 m s(-1)), trotted (4.1 m s(-1)) and cantered (7.0 m s(-1)) on a motorized treadmill. Over the range of gaits and speeds, DDF(sc) fascicles shortened while producing relatively low force, generating modest positive net work. In contrast, SDF fascicles initially shortened, then lengthened while producing high force, resulting in substantial negative net work. These findings suggest the long fibered, unipennate DDF(sc) supplements mechanical work during running, whereas the short fibered, multipennate SDF is specialized for economical high force and enhanced elastic energy storage. Apparent in vivo functions match well with the distinct architectural features of each muscle.     

Unusual gene order and organization of the sea urchin hox cluster

While the highly consistent gene order and axial colinear patterns of expression seem to be a feature of vertebrate hox gene clusters, this pattern may be less well conserved across the rest of the bilaterians. We report the first deuterostome instance of an intact hox cluster with a unique gene order where the paralog groups are not expressed in a sequential manner. The finished sequence from BAC clones from the genome of the sea urchin, Strongylocentrotus purpuratus, reveals a gene order wherein the anterior genes (Hox1, Hox2 and Hox3) lie nearest the posterior genes in the cluster such that the most 3' gene is Hox5. (The gene order is 5'-Hox1, 2, 3, 11/13c, 11/13b, 11/13a, 9/10, 8, 7, 6, 5-3'.) The finished sequence result is corroborated by restriction mapping evidence and BAC-end scaffold analyses. Comparisons with a putative ancestral deuterostome Hox gene cluster suggest that the rearrangements leading to the sea urchin gene order were many and complex.     

Latitudinal clines in body size,but not in thermal tolerance or heat‐shock cognate 70 (HSC70), in the highly‐dispersing intertidal gastropod Littorina keenae (Gastropoda: Littorinidae)

Natural populations of widely‐distributed animals often exhibit clinal variation in phenotypic traits or in allele frequencies of a particular gene over their geographical range. A planktotrophic intertidal snail, Littorina keenae is broadly distributed along the north‐eastern Pacific coast through a large latitudinal range (24°50′N–43°18′N). We tested for latitudinal clines in two complex phenotypic traits – thermal tolerance and body size – and one single locus trait – heat shock cognate 70 (HSC70) – in L. keenae along almost its entire geographical range. We found only weak evidence for a latitudinal cline in the thermal tolerance and no evidence for a cline in allele frequencies at HSC70. However, as predicted by Bergmann's rule, we detected a strong latitudinal cline that accounted for 60% of the variance in body size (R² = 0.598; P < 0.001). In contrast, body size did not significantly affect thermal tolerance. HSC70 showed no genetic differentiation among the populations, supporting our previous mitochondrial gene‐based estimate of high gene flow during this snail's free‐swimming larval stage. Given that L. keenae experiences panmixia along its species range, the observed size cline may be partially or entirely caused by a phenotypically plastic response to local thermal environments rather than by genetic divergence in body size among populations in response to locally optimizing natural selection. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 100 , 494–505.