Neuronal, affective, and sensory correlates of targeted helping behavior in male and female Sprague Dawley rats.

Introduction: Empathic behaviors are driven by the ability to understand the emotional states of others along with the motivation to improve it. Evidence points towards forms of empathy, like targeted helping, in many species including rats. There are several variables that may modulate targeted helping, including sex, sensory modalities, and activity of multiple neural substrates. Methods: Using a model of social contact-independent targeted helping, we first tested whether sex differences exist in helping behavior. Next, we explored sex differences in sensory and affective signaling, including direct visualization and an analysis of ultrasonic vocalizations made between animal pairs. Finally, we examined the neural activity in males and females of multiple regions of interest across time. Here, we aim to examine any behavioral differences in our lab's social contact independent targeted helping task between males and females. Results and Discussion: These findings are the first to intimate that, like other prosocial behaviors, males and females may exhibit similar social-independent targeted helping behavior, but the underlying sensory communication in males and females may differ. In addition, this is the first set of experiments that explore the neural correlates of social-independent targeted helping in both males and females. These results lay the groundwork for future studies to explore the similarities and differences that drive targeted helping in both sexes.

Rooting Species Trees Using Gene Tree-Species Tree Reconciliation.

Interpreting phylogenetic trees requires a root, which provides the direction of evolution and polarizes ancestor-descendant relationships. But inferring the root using genetic data is difficult, particularly in cases where the closest available outgroup is only distantly related, which are common for microbes. In this chapter, we present a workflow for estimating rooted species trees and the evolutionary history of the gene families that evolve within them using probabilistic gene tree-species tree reconciliation. We illustrate the pipeline using a small dataset of prokaryotic genomes, for which the example scripts can be run using modest computer resources. We describe the rooting method used in this work in the context or other rooting strategies and discuss some of the limitations and opportunities presented by probabilistic gene tree-species tree reconciliation methods.

Divergent evolutionary trajectories of bryophytes and tracheophytes from a complex common ancestor of land plants.

The origin of plants and their colonization of land fundamentally transformed the terrestrial environment. Here we elucidate the basis of this formative episode in Earth history through patterns of lineage, gene and genome evolution. We use new fossil calibrations, a relative clade age calibration (informed by horizontal gene transfer) and new phylogenomic methods for mapping gene family origins. Distinct rooting strategies resolve tracheophytes (vascular plants) and bryophytes (non-vascular plants) as monophyletic sister groups that diverged during the Cambrian, 515-494 million years ago. The embryophyte stem is characterized by a burst of gene innovation, while bryophytes subsequently experienced an equally dramatic episode of reductive genome evolution in which they lost genes associated with the elaboration of vasculature and the stomatal complex. Overall, our analyses reveal that extant tracheophytes and bryophytes are both highly derived from a more complex ancestral land plant. Understanding the origin of land plants requires tracing character evolution across a diversity of modern lineages.

The origin and evolution of stomata.

The acquisition of stomata is one of the key innovations that led to the colonisation of the terrestrial environment by the earliest land plants. However, our understanding of the origin, evolution and the ancestral function of stomata is incomplete. Phylogenomic analyses indicate that, firstly, stomata are ancient structures, present in the common ancestor of land plants, prior to the divergence of bryophytes and tracheophytes and, secondly, there has been reductive stomatal evolution, especially in the bryophytes (with complete loss in the liverworts). From a review of the evidence, we conclude that the capacity of stomata to open and close in response to signals such as ABA, CO2 and light (hydroactive movement) is an ancestral state, is present in all lineages and likely predates the divergence of the bryophytes and tracheophytes. We reject the hypothesis that hydroactive movement was acquired with the emergence of the gymnosperms. We also conclude that the role of stomata in the earliest land plants was to optimise carbon gain per unit water loss. There remain many other unanswered questions concerning the evolution and especially the origin of stomata. To address these questions, it will be necessary to: find more fossils representing the earliest land plants, revisit the existing early land plant fossil record in the light of novel phylogenomic hypotheses and carry out more functional studies that include both tracheophytes and bryophytes.

The role of the anterior insular during targeted helping behavior in male rats.

Empathy, the understanding of the emotional state of others, can be examined across species using the Perception Action Model, where shared affect promotes an action by "Observers" to aid a distressed "Target". The anterior insula (AI) has garnered interest in empathic behavior due to its role integrating sensory and emotional information of self and other. In the following studies, the AI was inhibited pharmacologically and chemogenetically during targeted helping. We demonstrate the insula is active during, and is necessary for the maintenance of, targeted helping. Analysis of ultrasonic vocalizations revealed distress calls from Targets increased when Observers' helping was attenuated due to insula inhibition. Targets' elevated distress was directly correlated to Observers' diminished helping behavior, suggesting emotional transfer between Observer and Target is blunted following Observer AI inhibition. Finally, the AI may selectively blunt targeted helping, as social exploration did not change in a social reward place conditioning task. These studies help further establish the anterior insula as a critical node in the empathic brain during targeted helping, even in the absence of direct social contact.

Wingtip folds and ripples on saturniid moths create decoy echoes against bat biosonar.

Sensory coevolution has equipped certain moth species with passive acoustic defenses to counter predation by echolocating bats.1,2 Some large silkmoths (Saturniidae) possess curved and twisted biosonar decoys at the tip of elongated hindwing tails.3,4 These are thought to create strong echoes that deflect biosonar-guided bat attacks away from the moth's body to less essential parts of their anatomy. We found that closely related silkmoths lacking such hindwing decoys instead often possess intriguing ripples and folds on the conspicuously lobed tips of their forewings. The striking analogy of twisted shapes displayed far from the body suggests these forewing structures might function as alternative acoustic decoys. Here we reveal that acoustic reflectivity and hence detectability of such wingtips is higher than that of the body at ultrasonic frequencies used by hunting bats. Wingtip reflectivity is higher the more elaborate the structure and the further from the body. Importantly, wingtip reflectivity is often considerably higher than in a well-studied functional hindwing decoy. Such increased reflectivity would misdirect the bat's sonar-guided attack toward the wingtip, resulting in similar fitness benefits to hindwing acoustic decoys. Structurally, folded wingtips present echo-generating surfaces to many directions, and folds and ripples can act as retroreflectors that together create conspicuous targets. Phylogenetically, folds and ripples at wingtips have evolved multiple times independently within silkmoths and always as alternatives to hindwing decoys. We conclude that they function as acoustic wingtip decoys against bat biosonar. VIDEO ABSTRACT.

Phylogenomic Evidence for the Monophyly of Bryophytes and the Reductive Evolution of Stomata.

The origin of land plants was accompanied by new adaptations to life on land, including the evolution of stomata-pores on the surface of plants that regulate gas exchange. The genes that underpin the development and function of stomata have been extensively studied in model angiosperms, such as Arabidopsis. However, little is known about stomata in bryophytes, and their evolutionary origins and ancestral function remain poorly understood. Here, we resolve the position of bryophytes in the land plant tree and investigate the evolutionary origins of genes that specify stomatal development and function. Our analyses recover bryophyte monophyly and demonstrate that the guard cell toolkit is more ancient than has been appreciated previously. We show that a range of core guard cell genes, including SPCH/MUTE, SMF, and FAMA, map back to the common ancestor of embryophytes or even earlier. These analyses suggest that the first embryophytes possessed stomata that were more sophisticated than previously envisioned and that the stomata of bryophytes have undergone reductive evolution, including their complete loss from liverworts.

Optimization of Spectral String Data Analysis Using a Binomial Discriminator for Weak-source Detection Decisions.

Operational health physics applications, such as radiological and nuclear monitoring and detection for homeland security or radiation protection purposes, generate time sequences of independent individual measurement data. Statistical algorithms have been developed that use the analysis of patterns in the data strings to enhance the test statistic for the decision on the absence or presence of a radiation source. These hypothesis test procedures have been applied to spectral data and have been optimized for the highest rate of correct identification of a weak Cs source at constant false positive detection rates. Optimization of correct detection decisions was investigated for various string data sequence lengths and for the regions of interest in the gamma spectrum. The highest correct source identification is achieved for string data analyses of the spectral contributions that maximize a [INCREMENT]µ/σ criterion, including energy regions around and containing the photopeak, but potentially also regions in the gamma spectrum other than those photopeak energies.

Low-Fidelity Spectral Analysis Utilizing a Binomial Discriminator for Weak-Source Detection Decisions.

The identification of radiological sources by analysis of a gamma spectrum usually relies on the location of the set of radionuclide-specific electron energies corresponding to the incident photons interacting by photoelectric absorption in the detection medium. The challenge in low-level detection applications is the identification of these "photopeaks" above the background counts registered in the detector from the natural radiation environment and system noise. For source detection decisions, regions of the gamma spectrum other than at the photopeak energies may provide additional information about the presence of a source and allow for a higher rate of correct identification of a weak source. A statistical algorithm utilizing low-fidelity spectral data partitioned into three distinct regions and employing a binomial discriminator was tested in a laboratory setting against the traditional approach of source identification by exceeding a decision threshold within the photopeak region of interest. For an unshielded Cs source with no significant scatter between the source and the detector, the traditional peak identification method performs as well or better than most algorithm settings for various source strengths. However, an algorithm which also includes information in the energy range of Compton scattered photons provides improved detection capabilities for shielded weak sources. Such algorithms, including higher-fidelity developments, could be deployed to improve current tools for the search for orphan radiological sources and in the characterization of low-level environmental contamination.

Enhancing Test Statistics by Utilizing Data Patterns in Sequential Measurement Strings in Radiation Detection.

Operational health physics applications, such as radiological and nuclear monitoring and detection for homeland security or radiation protection purposes, generate time sequences of independent individual measurement data. Statistical algorithms have been developed that utilize the analysis of patterns in data strings to enhance the test statistic for the decision on the absence or presence of a radiological source. Theoretical expectations have been verified in laboratory measurements for various lengths of data strings. Null hypothesis test performance and source detection efficacy have been shown to improve compared to the traditional method of achieving a detection decision by the comparison of a measured value to a fixed decision threshold.

Synthesis and SAR of selective muscarinic acetylcholine receptor subtype 1 (M1 mAChR) antagonists.

This Letter describes the synthesis and SAR, developed through an iterative analogue library approach, of a novel series of selective M1 mAChR antagonists for the potential treatment of Parkinson's disease, dystonia and other movement disorders. Compounds in this series possess M1 antagonist IC(50)s in the 441nM-19microM range with 8- to >340-fold functional selectivity versus rM2-rM5.

Implementing clinical practice guidelines: a community-based audit of breast cancer treatment. Australian Capital Territory and South Eastern New South Wales Breast Cancer Treatment Group.

OBJECTIVE: To improve breast cancer management by facilitating implementation of treatment guidelines. DESIGN: A prospective, longitudinal study (developed by clinicians and consumers) of all patients with newly diagnosed breast cancer. Four locally agreed breast cancer management guidelines were established (based on 1995 National Health and Medical Research Council guidelines) as practice indicators. SETTING: Breast cancer treatment facilities and medical practices in the Australian Capital Territory and South Eastern New South Wales, May 1997 to July 1998. MAIN OUTCOME MEASURES: Actual treatment received by patients for primary breast cancer during the study period. RESULTS: During the 14 months of the study, 19 clinicians registered 221 new patients with a proven diagnosis of breast cancer. Of 191 women with localised invasive breast cancer, 112 (59%) had tumours 2 cm or less in diameter. Axillary surgery in 173 (91%) of these women showed 107 (56%) had no axillary lymph node involvement. Of 87 women treated with breast-conserving surgery for locally invasive cancer, 85 (98%) also received postoperative radiotherapy. Some form of systemic adjuvant therapy was indicated in 99 women (axillary nodes positive or tumours > 2 cm diameter) and this treatment was received by 95 (96%). All 27 women aged under 50 years with node-positive disease received adjuvant chemotherapy. CONCLUSIONS: Enhancing uptake of breast cancer management guidelines is feasible at a regional level with an audit program and broad support among clinicians and consumers.

Decreased vascular permeability response to substance P in airways of genetically hypertensive rats.

1. The inbred genetically hypertensive strain (GH) of the Otago Wistar rat possesses more sensory neurons containing the neuropeptide substance P (SP) than does its genetically related control normotensive strain. 2. As SP contributes to airway inflammation by increasing microvascular permeability, we assessed the extravasation of Evans Blue dye in trachea and main bronchus of anaesthetized GH and control rats, in the presence of endogenous (capsaicin-liberated) or exogenous SP. 3. Following intravenous administration of either capsaicin (75 microg kg(-1)) or SP (3.3 nmol kg(-1)), extravasation of Evans Blue in airways from GH rats was only about 60% of that in airways of control rats. This difference was not gender-specific and responses to capsaicin were abolished by pretreatment with a selective NK1 receptor antagonist SR 140333 (360 nmol kg(-1)). 4. By contrast, the extravasation of dye caused by intravenous 5-hydroxytryptamine (0.5 micromol kg(-1)) was similar in magnitude in both GH and control strains. 5. Falls in systemic arterial blood pressure in response to exogenous SP (0.1-3 nmol kg(-1)) or acetylcholine (0.2-2 nmol kg(-1)) were also very similar between strains, but those in response to capsaicin (75 microg kg(-1)) in the GH rats were about double those in control rats. The hypotensive response to SP was abolished by SR 140333, but that to capsaicin was unaffected. 6. Our results indicate that the increased peripheral innervation density by SP-nerves in GH rats is accompanied by reduced inflammatory responses to SP. This does not involve decreased vasodilator potency of SP and is therefore probably related to altered endothelial responsiveness.

Love and friendship.

People with learning disabilities need to know about sexual health issues, and HIV/AIDS in particular. But how to convey complex and sensitive information in a clear and simple written format? Joëlle Brogan shows it can be done.

Construction of pYGK, an Actinobacillus actinomycetemcomitans-Escherichia coli shuttle vector.

A shuttle vector that is capable of replicating in Actinobacillus actinomycetemcomitans (Aa) and Escherichia coli (Ec) was constructed by modifying the Actinobacillus pleuropneumoniae (Ap) plasmid pYG53. A DNA fragment containing the KmR gene was inserted into pYG53 to generate pYGK, which confers resistance to kanamycin in both Aa and Ec. By electroporation, Ec DH5alpha and 17 strains of Aa were transformed with pYGK with efficiencies ranging from 0.5 to 3 X 10(6) colonies per microgram of DNA. Plasmid pYGK exists at approx. 3-4 copies per cell in Ec. This plasmid will facilitate the genetic manipulation of Aa strains and the molecular analysis of virulence factors expressed by this organism.

Development of a diagnostic polymerase chain reaction assay for detection of Mycoplasma hominis.

A polymerase chain reaction (PCR)-based assay was developed for the detection of Mycoplasma hominis. This assay generates a 152-bp PCR product which was part of an initial 471-bp M. hominis genomic DNA fragment. The 471-bp DNA fragment was shown by hybridization analysis to be unique for M. hominis. The PCR assay can amplify as few as 18 molecules of target DNA. This diagnostic assay offers potential for wide clinical application as it is rapid and can be successfully performed on crude sample preparations from a variety of media or biopsies. The use of this assay should aid in defining the aetiologic and pathologic roles played by M. hominis and thereby benefit patients.

Regulation of Actinobacillus actinomycetemcomitans leukotoxin expression: analysis of the promoter regions of leukotoxic and minimally leukotoxic strains.

The leukotoxin of Actinobacillus actinomycetemcomitans has been implicated as a virulence determinant in various human infections and is encoded by a multigene operon consisting of four known genes, designated ltxC, ltxA, ltxB, and ltxD. The ltx operon appears to be present in all A. actinomycetemcomitans strains, but levels of toxin expression vary greatly among strains. Thus, to gain a better understanding of the expression and regulation of the ltx operon, we have analyzed the ltx promoters of a highly toxic (JP2) and a minimally toxic (652) strain of A. actinomycetemcomitans. The nucleotide sequence of the JP2 ltx promoter contains -10 and -35 elements situated 350 bases upstream of ltxC, and primer extension of JP2 RNA confirmed that they are functional in vivo. However, a second primer extension product of 40 bases was present, and analysis of a series of truncated JP2 promoters fused to lacZ suggested that the region immediately upstream of ltxC also promotes transcription in Escherichia coli. These results suggest that two promoters may direct ltx expression in JP2. In addition, a small open reading frame capable of encoding a peptide of 78 amino acids was identified upstream of ltxC. Northern blots showed that this open reading frame is transcribed as part of a 4.2-kb mRNA, a transcript not previously identified as being derived from the ltx operon. In contrast, strain 652 expresses low steady-state levels of ltx mRNA, and its intact ltx promoter was inefficient in transcribing lacZ in E. coli. The nucleotide sequence of the 652 promoter is similar to that of the JP2 promoter but contains a region of 530 bp that is not present in JP2. Of 15 additional strains of A. actinomycetemcomitans that were analyzed, 13 contained promoters resembling the 652 sequence and 2 possessed JP2-like promoters. Both strains possessing the JP2-like promoter expressed 10- to 20-fold-higher levels of leukotoxin than did the strains possessing promoters resembling the 652 promoter. These results suggest that high levels of leukotoxin expression may correlate with the presence of the JP2-like promoter.

Development of a DNA probe for Ureaplasma urealyticum.

Ureaplasma urealyticum has been associated with a variety of disease conditions in humans. However, its exact etiologic role has not been well established because of the difficulties encountered in cultural diagnosis and the time needed for positive identifications. A DNA probe which is specific for a target DNA sequence unique to this suspected pathogen offers a rapid, sensitive and specific means of diagnosis. This study details the development of a polymerase chain reaction system for U. urealyticum. Using conventional hybridization techniques, a cloned genomic fragment was found to be specific for this organism. Sequencing of part of this probe DNA permitted the assignment of oligonucleotide primers which amplified a 186 bp target segment. This PCR system is specific for U. urealyticum but not for other closely related species of mycoplasma. This highly sensitive diagnostic technique will aid in determining the etiologic role, tissue tropism and dynamics of pathogenesis of this organism, and thereby result in better patient care.

Sorting out the cephalosporins.

How can you choose the best cephalosporin to prescribe out of an array that is vast and quickly growing? Dr Brogan simplifies the process by describing the specific advantages as well as the shortcomings of individual agents. He also makes general recommendations based on his experience.