Dopamine mediates context-dependent modulation of sensory plasticity in C. elegans

Dopamine has been implicated in the modulation of diverse forms of behavioral plasticity, including appetitive learning and addiction. An important challenge is to understand how dopamine's effects at the cellular level alter the properties of neural circuits to modify behavior. In the nematode C. elegans, dopamine modulates habituation of an escape reflex triggered by body touch. In the absence of food, animals habituate more rapidly than in the presence of food; this contextual information about food availability is provided by dopaminergic mechanosensory neurons that sense the presence of bacteria. We find that dopamine alters habituation kinetics by selectively modulating the touch responses of the anterior-body mechanoreceptors; this modulation involves a D1-like dopamine receptor, a Gq/PLC-beta signaling pathway, and calcium release within the touch neurons. Interestingly, the body touch mechanoreceptors can themselves excite the dopamine neurons, forming a positive feedback loop capable of integrating context and experience to modulate mechanosensory attention.     

Quality control of human tissues-experience from the Indiana University Cancer Center-Lilly Research Labs human tissue bank

The success of molecular research and its applications in both the clinical and basic research arenas is strongly dependent on the collection, handling, storage, and quality control of fresh human tissue samples. This tissue bank was set up to bank fresh surgically obtained human tissue using a Clinical Annotated Tissue Database (CATD) in order to capture the associated patient clinical data and demographics using a one way patient encryption scheme to protect patient identification. In this study, we determined that high quality of tissue samples is imperative for both genomic and proteomic molecular research. This paper also contains a brief compilation of the literature involved in the patient ethics, patient informed consent, patient de-identification, tissue collection, processing, and storage as well as basic molecular research generated from the tissue bank using good clinical practices. The current applicable rules, regulations, and guidelines for handling human tissues are briefly discussed. More than 6,610 cancer patients have been consented (97% of those that were contacted by the consenter) and 16,800 tissue specimens have been banked from these patients in 9 years. All samples collected in the bank were QC’d by a pathologist. Approximately 1,550 tissue samples have been requested for use in basic, clinical, and/or biomarker cancer research studies. Each tissue aliquot removed from the bank for a research study were evaluated by a second H&E, if the samples passed the QC, they were submitted for genomic and proteomic molecular analysis/study. Approximately 75% of samples evaluated were of high histologic quality and used for research studies. Since 2003, we changed the patient informed consent to allow the tissue bank to gather more patient clinical follow-up information. Ninety two percent of the patients (1,865 patients) signed the new informed consent form and agreed to be re-contacted for follow-up information on their disease state. In addition, eighty five percent of patients (1,584) agreed to be re-contacted to provide a biological fluid sample to be used for biomarker research.     

Checkpoint independence of most DNA replication origins in fission yeast

Background

In budding yeast, the replication checkpoint slows progress through S phase by inhibiting replication origin firing. In mammals, the replication checkpoint inhibits both origin firing and replication fork movement. To find out which strategy is employed in the fission yeast, Schizosaccharomyces pombe, we used microarrays to investigate the use of origins by wild-type and checkpoint-mutant strains in the presence of hydroxyurea (HU), which limits the pool of deoxyribonucleoside triphosphates (dNTPs) and activates the replication checkpoint. The checkpoint-mutant cells carried deletions either of rad3 (which encodes the fission yeast homologue of ATR) or cds1 (which encodes the fission yeast homologue of Chk2).

Results

Our microarray results proved to be largely consistent with those independently obtained and recently published by three other laboratories. However, we were able to reconcile differences between the previous studies regarding the extent to which fission yeast replication origins are affected by the replication checkpoint. We found (consistent with the three previous studies after appropriate interpretation) that, in surprising contrast to budding yeast, most fission yeast origins, including both early- and late-firing origins, are not significantly affected by checkpoint mutations during replication in the presence of HU. A few origins (~3%) behaved like those in budding yeast: they replicated earlier in the checkpoint mutants than in wild type. These were located primarily in the heterochromatic subtelomeric regions of chromosomes 1 and 2. Indeed, the subtelomeric regions defined by the strongest checkpoint restraint correspond precisely to previously mapped subtelomeric heterochromatin. This observation implies that subtelomeric heterochromatin in fission yeast differs from heterochromatin at centromeres, in the mating type region, and in ribosomal DNA, since these regions replicated at least as efficiently in wild-type cells as in checkpoint-mutant cells.

Conclusion

The fact that ~97% of fission yeast replication origins – both early and late – are not significantly affected by replication checkpoint mutations in HU-treated cells suggests that (i) most late-firing origins are restrained from firing in HU-treated cells by at least one checkpoint-independent mechanism, and (ii) checkpoint-dependent slowing of S phase in fission yeast when DNA is damaged may be accomplished primarily by the slowing of replication forks.     

Severe upper airway obstruction due to delayed retropharyngeal hematoma formation following blunt cervical trauma

Background

We report a case of severe upper airway obstruction due to a retropharyngeal hematoma that presented nearly one day after a precipitating traumatic injury. Retropharyngeal hematomas are rare, but may cause life-threatening airway compromise.

Case presentation

A 50 year-old man developed severe dyspnea with oropharyngeal airway compression due to retropharyngeal hematoma 20 hours after presenting to the emergency department. The patient also had a fractured first cervical vertebra and was diagnosed with a left brachial plexopathy. The patient underwent emergent awake fiberoptic endotracheal intubation to provide a definitive airway.

Conclusion

Retropharyngeal hematoma with life-threatening airway compromise can develop hours or days after a precipitating injury. Clinicians should be alert to the potential for this delayed airway collapse, and should also be prepared to rapidly secure the airway in this patient population likely to have concomitant cervical spinal or head injuries.     

Social,contextual, and individual factors affecting the occurrence and acoustic structure of drumming bouts in wild chimpanzees (Pan troglodytes)

The production of structured and repetitive sounds by striking objects is a behavior found not only in humans, but also in a variety of animal species, including chimpanzees (Pan troglodytes). In this study we examined individual and social factors that may influence the frequency with which individuals engage in drumming behavior when producing long distance pant hoot vocalizations, and analyzed the temporal structure of those drumming bouts. Male chimpanzees from Budongo Forest, Uganda, drummed significantly more frequently during travel than feeding or resting and older individuals were significantly more likely to produce drumming bouts than younger ones. In contrast, we found no evidence that the presence of estrus females, high ranking males and preferred social partners in the caller's vicinty had an effect on the frequency with which an individual accompanied their pant hoot vocalization with drumming. Through acoustic analyses, we demonstrated that drumming sequences produced with pant hoots may have contained information on individual identity and that qualitatively, there was individual variation in the complexity of the temporal patterns produced. We conclude that drumming patterns may act as individually distinctive long‐distance signals that, together with pant hoot vocalizations, function to coordinate the movement and spacing of dispersed individuals within a community, rather than as signals to group members in the immediate audience. Am J Phys Anthropol 156:125–134, 2015 © 2014 Wiley Periodicals, Inc.     

Modeling the Ecological and Phenological Predictors of Fruit Consumption by Gibbons (Hylobates albibarbis)

Understanding the ecological interactions between plant reproductive strategies and frugivore feeding behavior can offer insight into the maintenance of tropical forest biodiversity. We examined the role of plant ecological and phenological characteristics in influencing fruit consumption by the White‐bearded gibbon (Hylobates albibarbis) in Gunung Palung National Park, Indonesian Borneo. Gibbons are widespread across Borneo, highly frugivorous and perform important seed dispersal services. We compare multiple models using information criteria to identify the ecological and phenological predictors that most strongly influence gibbon fruit use of 154 plant genera. The most important predictors of resource use were the overall abundance of a genus and the consistency of fruit availability. Plant genera can maintain constant fruit availability as a result of (1) individual stems fruiting often or (2) stems fruiting out of synchrony with each other (asynchrony). Our results demonstrate that gibbons prefer to feed on plant genera that provide consistent fruit availability due to fruiting asynchrony. Because gibbons feed more often on genera that fruit asynchronously, gibbons are more likely to disperse seeds of plant genera with this reproductive strategy. Research on other frugivorous species is needed to determine whether the results for gibbons are generalizable more broadly. Finally, these results suggest that asynchronously fruiting plant genera may be particularly important for habitat restoration in tropical forests designed for frugivore conservation.     

Functional Roles of Clusters of Hydrophobic and Polar Residues in the Epithelial Na+ Channel Knuckle Domain

The extracellular regions of epithelial Na⁺ channel subunits are highly ordered structures composed of domains formed by α helices and β strands. Deletion of the peripheral knuckle domain of the α subunit in the αβγ trimer results in channel activation, reflecting an increase in channel open probability due to a loss of the inhibitory effect of external Na⁺ (Na⁺ self-inhibition). In contrast, deletion of either the β or γ subunit knuckle domain within the αβγ trimer dramatically reduces epithelial Na⁺ channel function and surface expression, and impairs subunit maturation. We systematically mutated individual α subunit knuckle domain residues and assessed functional properties of these mutants. Cysteine substitutions at 14 of 28 residues significantly suppressed Na⁺ self-inhibition. The side chains of a cluster of these residues are non-polar and are predicted to be directed toward the palm domain, whereas a group of polar residues are predicted to orient their side chains toward the space between the knuckle and finger domains. Among the mutants causing the greatest suppression of Na⁺ self-inhibition were αP521C, αI529C, and αS534C. The introduction of Cys residues at homologous sites within either the β or γ subunit knuckle domain resulted in little or no change in Na⁺ self-inhibition. Our results suggest that multiple residues in the α subunit knuckle domain contribute to the mechanism of Na⁺ self-inhibition by interacting with palm and finger domain residues via two separate and chemically distinct motifs.