AKT constitutes a signal-promoted alternative exon-junction complex that regulates nonsense-mediated mRNA decay.

Despite a long appreciation for the role of nonsense-mediated mRNA decay (NMD) in destroying faulty, disease-causing mRNAs and maintaining normal, physiologic mRNA abundance, additional effectors that regulate NMD activity in mammalian cells continue to be identified. Here, we describe a haploid-cell genetic screen for NMD effectors that has unexpectedly identified 13 proteins constituting the AKT signaling pathway. We show that AKT supersedes UPF2 in exon-junction complexes (EJCs) that are devoid of RNPS1 but contain CASC3, defining an unanticipated insulin-stimulated EJC. Without altering UPF1 RNA binding or ATPase activity, AKT-mediated phosphorylation of the UPF1 CH domain at T151 augments UPF1 helicase activity, which is critical for NMD and also decreases the dependence of helicase activity on ATP. We demonstrate that upregulation of AKT signaling contributes to the hyperactivation of NMD that typifies Fragile X syndrome, as exemplified using FMR1-KO neural stem cells derived from induced pluripotent stem cells.

Enhanced polyubiquitination of Shank3 and NMDA receptor in a mouse model of autism.

We have created a mouse genetic model that mimics a human mutation of Shank3 that deletes the C terminus and is associated with autism. Expressed as a single copy [Shank3(+/ΔC) mice], Shank3ΔC protein interacts with the wild-type (WT) gene product and results in >90% reduction of Shank3 at synapses. This "gain-of-function" phenotype is linked to increased polyubiquitination of WT Shank3 and its redistribution into proteasomes. Similarly, the NR1 subunit of the NMDA receptor is reduced at synapses with increased polyubiquitination. Assays of postsynaptic density proteins, spine morphology, and synapse number are unchanged in Shank3(+/ΔC) mice, but the amplitude of NMDAR responses is reduced together with reduced NMDAR-dependent LTP and LTD. Reciprocally, mGluR-dependent LTD is markedly enhanced. Shank3(+/ΔC) mice show behavioral deficits suggestive of autism and reduced NMDA receptor function. These studies reveal a mechanism distinct from haploinsufficiency by which mutations of Shank3 can evoke an autism-like disorder.

Does timing of total elbow arthroplasty after distal humerus fracture affect 2-year complication rates?

BACKGROUND: Open reduction and internal fixation (ORIF) remains the gold standard for adult distal humerus fractures (DHF). However, indications for total elbow arthroplasty (TEA) continue to expand and the incidence of primary and salvage TEA for DHF has increased. The objective of this study was to compare complication and reoperation rate for acute vs. delayed primary and salvage TEA performed for DHF. METHODS: Patients who underwent TEA for DHF were identified in the PearlDiver database. Patients were sorted into 3 cohorts: (1) acute TEA (within 2 weeks of diagnosis), (2) delayed TEA (between 2 weeks and 6 months after diagnosis), and (3) salvage TEA (after failed ORIF, malunion, nonunion, delayed treatment between 6 months and 1 year or post-traumatic arthritis). Multivariate analysis was used to assess for confounding variables and covariates when identifying differences in complications between cohorts. RESULTS: A total of 788 patients underwent acute TEA, 213 patients underwent delayed TEA, and 422 patients underwent salvage TEA after DHF. The incidence of periprosthetic joint infection (PJI) (8.5% vs. 3.4%, odds ratio [OR] 2.60, P = .002) and triceps injury (2.4% vs. 0.4%, OR 6.29, P = .012) were higher in the delayed compared to acute cohort. The incidence of revision (8.5% vs. 2.1%, OR 3.76, P < 0.001), periprosthetic fracture (4.3% vs. 1.1%, OR 3.64, P = .002), PJI (14.7% vs 3.4%, OR 4.36, P < .001), triceps injury (2.6% vs. 0.4%, OR 5.70, P = .008), and wound complications (6.9% vs 2.9%, OR 2.33, P = .002) were higher in the salvage compared to acute cohort. There was an increased rate of revision (8.5% vs. 1.9%, OR 6.08, P = .002) in the salvage compared to delayed cohort. CONCLUSION: Patients undergoing salvage TEA after DHF have increased rates of revision, periprosthetic fracture, PJI, triceps injury, and wound complications at 2 years post-operatively. The salvage cohort also had an increased risk of revision when compared to the delayed cohort. However, other than revision rates, patients in the salvage and delayed cohorts have similar postoperative complication rates.

Repeat RNA expansion disorders of the nervous system: post-transcriptional mechanisms and therapeutic strategies.

Dozens of incurable neurological disorders result from expansion of short repeat sequences in both coding and non-coding regions of the transcriptome. Short repeat expansions underlie microsatellite repeat expansion (MRE) disorders including myotonic dystrophy (DM1, CUG50-3,500 in DMPK; DM2, CCTG75-11,000 in ZNF9), fragile X tremor ataxia syndrome (FXTAS, CGG50-200 in FMR1), spinal bulbar muscular atrophy (SBMA, CAG40-55 in AR), Huntington's disease (HD, CAG36-121 in HTT), C9ORF72- amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD and C9-ALS/FTD, GGGGCC in C9ORF72), and many others, like ataxias. Recent research has highlighted several mechanisms that may contribute to pathology in this heterogeneous class of neurological MRE disorders - bidirectional transcription, intranuclear RNA foci, and repeat associated non-AUG (RAN) translation - which are the subject of this review. Additionally, many MRE disorders share similar underlying molecular pathologies that have been recently targeted in experimental and preclinical contexts. We discuss the therapeutic potential of versatile therapeutic strategies that may selectively target disrupted RNA-based processes and may be readily adaptable for the treatment of multiple MRE disorders. Collectively, the strategies under consideration for treatment of multiple MRE disorders include reducing levels of toxic RNA, preventing RNA foci formation, and eliminating the downstream cellular toxicity associated with peptide repeats produced by RAN translation. While treatments are still lacking for the majority of MRE disorders, several promising therapeutic strategies have emerged and will be evaluated within this review.

Robotic Placement of 3 Trans-Sacral TransiIliac Screws Through a Single Corridor for U-Type Sacrum Fracture: A Case Report.

CASE: We present a case of robot-assisted placement of 3 trans-sacral transiliac screws through a single corridor for an unstable U-type sacral fracture in a 95-year-old woman. She had persistent pain and inability to mobilize with physical therapy. At 3-month follow-up, the patient had evidence of interval healing and stable hardware and was able to return to her prior functional baseline. CONCLUSION: We demonstrate successful utilization of robotics to place 3 trans-sacral transiliac screws in a single corridor for fixation of an unstable pelvic ring injury. This technique was used to overcome challenges with visualization and implant placement.

Timing of Olecranon Fracture Fixation Does Not Affect Early Complication or Reoperation Rates.

Purpose: Surgical fixation of olecranon fractures can lead to soft-tissue complications and return to the operating room for hardware removal. While some risk factors of complications after olecranon fracture fixation have been described, the effects of fixation timing on complications and reoperation have not been evaluated. The purpose of the present study was to assess whether the timing of olecranon fracture fixation affects complication and reoperation rates. Methods: All patients who underwent olecranon fracture open reduction and internal fixation at a single level 1 trauma center from January 2012 to February 2022 were included in the study. A retrospective review was performed to evaluate patients for inclusion and to identify patient demographic factors, medical comorbidities, concomitant injuries, mechanism of injury, and time to fixation. Operative and clinical notes were evaluated to identify fixation type and outcomes of interest. Patients were stratified into early, standard, and delayed fixation groups (0-3 days, 4-14 days, and >14 days, respectively) for independent analyses, and Fisher's exact test was used to identify differences in complications and reoperations between groups. Multivariate analysis was used to assess associations between patient demographic factors, complication rates, and time to surgery. Results: A total of 97 patients met inclusion criteria of having an olecranon open reduction and internal fixation and had a minimum follow-up of at least 10 weeks, with an average follow-up of 7.1 months. The average time to surgery in the overall cohort was 9.3 days. There were no differences in the number of total complications and rate of reoperation among the three cohorts. Smoking was found to be significantly associated with total complications, while open fracture was significantly associated with reoperation. Polytrauma and open fracture were significantly associated with earlier operation, while smoking was significantly associated with delayed fixation. Conclusions: The timing of fixation of displaced olecranon fractures does not significantly increase the rate of early complications or reoperation. Type of study/level of evidence: Symptom Prevalence Study III.

C-Reactive Protein Does Not Predict Future Depression Onset in Adolescents: Preliminary Findings from a Longitudinal Study.

Introduction: Neuroinflammatory processes have been extensively implicated in the underlying neurobiology of numerous neuropsychiatric disorders. Elevated C-reactive protein (CRP), an indicator of nonspecific inflammation commonly utilized in clinical practice, has been associated with depression in adults. In adolescents, our group previously found CRP to be associated with altered neural reward function but not with mood and anxiety symptoms assessed cross-sectionally. We hypothesized that the distinct CRP findings in adolescent versus adult depression may be due to chronicity, with neuroinflammatory effects on psychiatric disorders gradually accumulating over time. Here, we conducted a longitudinal study to evaluate if CRP levels predicted future onset or progression of depression in adolescents. Methods: Participants were 53 adolescents (age = 14.74 ± 1.92 years, 35 female), 40 with psychiatric symptoms and 13 healthy controls. At baseline, participants completed semistructured diagnostic evaluations; dimensional assessments for anxiety, depression, anhedonia, and suicidality severity; and bloodwork to quantify CRP levels. Clinical assessments were repeated at longitudinal follow-up after ∼1.5 years. Spearman's correlation between CRP levels and follow-up symptom severity were controlled for body mass index, age, sex, and follow-up interval and considered significant at the two-tailed, Bonferroni-adjusted p < 0.05 level. Results: After correction for multiple comparisons, no relationships were identified between baseline CRP levels and follow-up symptom severity. Conclusion: CRP levels were not significantly associated with future psychiatric symptoms in adolescents in this preliminary analysis. This may suggest that CRP is not a useful biomarker for adolescent depression and anxiety. However, future longitudinal studies with larger sample sizes and incorporating additional indicators of neuroinflammation are needed.

Association of Timing of Hindfoot Arthrodesis and Early Reoperation Rates for Total Ankle Arthroplasty.

BACKGROUND: Prior literature has demonstrated that ipsilateral hindfoot arthrodesis may increase the risk for reoperation after total ankle arthroplasty (TAA) and that simultaneous hindfoot arthrodesis with TAA could result in short-term clinical and radiologic improvements. The purpose of this study is to compare the reoperation rates after TAA with prior hindfoot arthrodesis vs simultaneous arthrodesis and TAA. METHODS: Patients who underwent primary TAA were identified in the PearlDiver database. Patients were sorted into 2 study cohorts: hindfoot arthrodesis prior to TAA and simultaneous arthrodesis and TAA. Propensity matched control cohorts were identified for each study group. Multivariate analysis was conducted to account for any confounding variables and covariates when identifying differences in complications between cohorts. RESULTS: 297 patients underwent TAA with prior hindfoot arthrodesis and 174 underwent TAA and hindfoot arthrodesis concurrently. The incidence of reoperation (13.8% vs 5.2%, P < .001) and infection (12.6% vs 5.9%, P = .011) for the simultaneous cohort was higher when compared to the matched control cohort. In contrast, there was no statistically significant difference when comparing the prior arthrodesis cohort to the matched control cohort in reoperation rates (5.1% vs 4.7%, P = .787) or infection rates (4.4% vs 4.8%, P = .734). Those undergoing simultaneous procedures had increased incidences of reoperation, wound complications, infection, and emergency department visits (P < .0167) when compared to the TAA with prior arthrodesis cohort. CONCLUSION: Patients undergoing TAA and hindfoot arthrodesis concurrently were found to have higher rates of reoperation and infection when compared to the matched control cohort . In contrast, there was no difference in these rates in patients undergoing TAA with prior hindfoot arthrodesis compared with their matched control cohort. Patients undergoing simultaneous procedures had increased rates of reoperations, wound complications, infection, and emergency department visits compared to the TAA with prior arthrodesis cohort.

Immunological correlates of suicidality among adolescents with internalizing symptoms.

Background: Suicide is a leading cause of death in adolescents and young adults globally. Well-established risk factors for suicide are depression and past suicide attempts. People experiencing suicidality may represent a distinct neurobiological group of people with depression. Because converging evidence has implicated inflammation in depression, we sought to investigate relationships between suicidality and immune markers in youth experiencing diverse mood and anxiety symptoms. We hypothesized that adolescents with suicidality would exhibit a unique immune signature. Methods: Adolescents underwent semi-structured interviews and completed self-reported measures to assess psychopathology, including suicidality (suicidal ideation, plans, or attempts). Fasting blood samples were collected, cultured with and without lipopolysaccharide (LPS) to stimulate an inflammatory response, and analyzed for 41 immune analytes. To assess how immune function related to suicidality categorically and dimensionally, we conducted group comparisons and correlations while controlling for multiple comparisons using false discovery rate (FDR). To further uncover subtle immune-suicidality relationships, we employed a data-driven approach using factor analysis to extract major immune factors, each of which was subsequently correlated with suicidality measures. Results: Among 126 participants, 29 were healthy controls and 97 participants had internalizing symptoms; within the clinical group, 57 experienced suicidality. Three immune analytes differed between healthy controls, suicidal, and non-suicidal adolescents with internalizing symptoms in the LPS condition: Flt-3L (p FDR = 0.0246), GM-CSF (p FDR = 0.0246), and IFN-γ (p FDR = 0.0246). These analytes were negatively correlated with the Beck Scale for Suicide Ideation (BSSI): Flt-3L (ρ = -0.19, p = 0.04); GM-CSF (ρ = -0.26, p = 0.004); IFN-γ (ρ =-0.33, p = 0.0003). GM-CSF also negatively correlated with number of suicide attempts (ρ = -0.39, p = 0.003). Factor analysis reduced 41 analytes to several common immune factors across experimental conditions, with Flt-3L, GM-CSF, and IFN-γ all loading heavily onto immune factors that were hypoactive in suicidality. Through this data-driven approach, we detected further associations between suicidality and immune factors across all conditions. Conclusions: Peripheral immune function may be distinctly altered in adolescent suicidality. Future work should examine immune-suicidality relationships longitudinally.

Mycobacterium tuberculosis infectious monoarthritis in a paediatric patient.

Mycobacterium tuberculosis is uncommon in the USA, and when it is diagnosed, it is usually in adult patients with identifiable risk factors presenting with pulmonary manifestations of the disease. Paediatric tuberculosis is rare, and a minority of those cases can present with isolated extrapulmonary infection. When the musculoskeletal system is involved, there are often no constitutional symptoms, and it can resemble other infectious and inflammatory processes. Diagnosis is challenging, and delay leads to irreversible destructive osteoarticular changes. A prompt diagnosis requires a high index of suspicion. This report presents a case of successfully diagnosed paediatric M. tuberculosis monoarthritis of the knee to highlight these challenges.

C-reactive protein does not predict future depression onset in adolescents: preliminary findings from a longitudinal study.

Introduction: Neuroinflammatory processes have been extensively implicated in the underlying neurobiology of numerous neuropsychiatric disorders. Elevated C-reactive protein (CRP), an indicator of non-specific inflammation commonly utilized in clinical practice, has been associated with depression in adults. In adolescents, our group previously found CRP to be associated with altered neural reward function but not with mood and anxiety symptoms assessed cross-sectionally. We hypothesized that the distinct CRP findings in adolescent vs. adult depression may be due to chronicity, with neuroinflammatory effects on psychiatric disorders gradually accumulating over time. Here, we conducted a longitudinal study to evaluate if CRP levels predicted future onset or progression of depression in adolescents. Methods: Participants were 53 adolescents (ages 14.74 ± 1.92, 35 female), 40 with psychiatric symptoms and 13 healthy controls. At baseline, participants completed semi-structured diagnostic evaluations; dimensional assessments for anxiety, depression, anhedonia, and suicidality severity; and bloodwork to quantify CRP levels. Clinical assessments were repeated at longitudinal follow-up after approximately 1.5 years. Spearman's correlation between CRP levels and follow-up symptom severity were controlled for BMI, age, sex, and follow-up interval and considered significant at the two-tailed, Bonferroni-adjusted p < 0.05 level. Results: After correction for multiple comparisons, no relationships were identified between baseline CRP levels and follow-up symptom severity. Conclusion: CRP levels were not significantly associated with future psychiatric symptoms in adolescents in this preliminary analysis. This may suggest that CRP is not a useful biomarker for adolescent depression and anxiety. However, future longitudinal studies with larger sample sizes and incorporating additional indicators of neuroinflammation are needed.

Successfully Treated Upper-Extremity Necrotizing Fasciitis Caused by Photobacterium damselae.

Necrotizing fasciitis is a soft-tissue infection associated with significant morbidity and mortality. The bacteria most associated with necrotizing fasciitis include Streptococcus pyogenes (group A), Clostridium species, Streptococcus species, and Staphylococcus species. Photobacterium damselae (P. damselae), formerly known as Vibrio damselae, is a halophilic, gram-negative bacillus known to infect marine organisms in warm coastal waters. Necrotizing fasciitis associated with P. damselae has been reported to have higher rates of serious complications and mortality because of an atypical presentation and a rapidly progressive course. This report presents a case of successfully treated P. damselae necrotizing fasciitis of the upper extremity and the nuances of management that led to a favorable outcome in which the patient was discharged for home without complications.

Uterine administration of C-X-C motif chemokine ligand 12 increases the pregnancy rates in mice with induced endometriosis.

OBJECTIVE: To study the effect of intrauterine injection of C-X-C motif chemokine ligand 12 (CXCL12), also known as a stem cell chemoattractant (stromal cell-derived factor 1), on fertility and endometrial receptivity in mice with endometriosis. DESIGN: Laboratory study. SETTING: Academic Medical Center. ANIMAL(S): Fifty-six mice underwent chemotherapy and bone marrow transplantation. Thirty-six of these mice underwent either surgery to induce endometriosis (n = 20) or sham surgery (n = 16). INTERVENTION(S): Injection of CXCL12 as a potential therapeutic agent to improve fertility in endometriosis. MAIN OUTCOME MEASURE(S): Pregnancy rate, bone marrow-derived cell (BMDC) recruitment and endometrial receptivity markers. RESULT(S): The mice with or without endometriosis received a single uterine injection of either CXCL12 or placebo. Uterine injection of CXCL12 increased the pregnancy rates in a mouse model of endometriosis. Mice were euthanized after delivery, and implantation markers homeobox A11, alpha-v beta-3 integrin, and progesterone receptor were analyzed by immunohistochemistry, whereas green fluorescent protein positive BMDC recruitment was quantified by immunohistochemistry and immunofluorescence. The sham surgery groups without endometriosis had the highest cumulative pregnancy rate (100%) regardless of CXCL12 treatment. The endometriosis group treated with placebo had the lowest pregnancy rate. An increased pregnancy rate was noted in the endometriosis group after treatment with CXCL12. There was also an increase in BMDC recruitment and endometrial expression of progesterone receptor and alpha-v beta-3 integrin in the endometriosis group that received CXCL12 compared with that in the endometriosis group that received placebo. CONCLUSION(S): Uterine injection of CXCL12 increased the pregnancy rates in a mouse model of endometriosis. These results suggest that CXCL12 has a potential role as a therapeutic agent in women with infertility related to endometriosis and potentially other endometrial receptivity defects.

Magmatic surge requires two-stage model for the Laramide orogeny.

The Laramide orogeny is a pivotal time in the geological development of western North America, but its driving mechanism is controversial. Most prominent models suggest this event was caused by the collision of an oceanic plateau with the Southern California Batholith (SCB) which caused the angle of subduction beneath the continent to shallow and led to shut-down of the arc. Here, we use over 280 zircon and titanite Pb/U ages from the SCB to establish the timing and duration of magmatism, metamorphism and deformation. We show that magmatism was surging in the SCB from 90 to 70 Ma, the lower crust was hot, and cooling occurred after 75 Ma. These data contradict plateau underthrusting and flat-slab subduction as the driving mechanism for early Laramide deformation. We propose that the Laramide orogeny is a two-stage event consisting of: 1) an arc 'flare-up' phase in the SCB from 90-75 Ma; and 2) a widespread mountain building phase in the Laramide foreland belt from 75-50 Ma that is linked to subduction of an oceanic plateau.

MECP2-related pathways are dysregulated in a cortical organoid model of myotonic dystrophy.

Myotonic dystrophy type 1 (DM1) is a multisystem, autosomal-dominant inherited disorder caused by CTG microsatellite repeat expansions (MREs) in the 3' untranslated region of the dystrophia myotonica-protein kinase (DMPK) gene. Despite its prominence as the most common adult-onset muscular dystrophy, patients with congenital to juvenile-onset forms of DM1 can present with debilitating neurocognitive symptoms along the autism spectrum, characteristic of possible in utero cortical defects. However, the molecular mechanism by which CTG MREs lead to these developmental central nervous system (CNS) manifestations is unknown. Here, we showed that CUG foci found early in the maturation of three-dimensional (3D) cortical organoids from DM1 patient-derived induced pluripotent stem cells (iPSCs) cause hyperphosphorylation of CUGBP Elav-like family member 2 (CELF2) protein. Integrative single-cell RNA sequencing and enhanced cross-linking and immunoprecipitation (eCLIP) analysis revealed that reduced CELF2 protein-RNA substrate interactions results in misregulation of genes critical for excitatory synaptic signaling in glutamatergic neurons, including key components of the methyl-CpG binding protein 2 (MECP2) pathway. Comparisons to MECP2(y/-) cortical organoids revealed convergent molecular and cellular defects such as glutamate toxicity and neuronal loss. Our findings provide evidence suggesting that early-onset DM1 might involve neurodevelopmental disorder-associated pathways and identify N-methyl-d-aspartic acid (NMDA) antagonists as potential treatment avenues for neuronal defects in DM1.

Impact of fuel quality regulation and speed reductions on shipping emissions: implications for climate and air quality.

Atmospheric emissions of gas and particulate matter from a large ocean-going container vessel were sampled as it slowed and switched from high-sulfur to low-sulfur fuel as it transited into regulated coastal waters of California. Reduction in emission factors (EFs) of sulfur dioxide (SO2), particulate matter, particulate sulfate and cloud condensation nuclei were substantial (≥ 90%). EFs for particulate organic matter decreased by 70%. Black carbon (BC) EFs were reduced by 41%. When the measured emission reductions, brought about by compliance with the California fuel quality regulation and participation in the vessel speed reduction (VSR) program, are placed in a broader context, warming from reductions in the indirect effect of SO4 would dominate any radiative changes due to the emissions changes. Within regulated waters absolute emission reductions exceed 88% for almost all measured gas and particle phase species. The analysis presented provides direct estimations of the emissions reductions that can be realized by California fuel quality regulation and VSR program, in addition to providing new information relevant to potential health and climate impact of reduced fuel sulfur content, fuel quality and vessel speed reductions.

Reward function as an outcome predictor in youth with mood and anxiety symptoms.

BACKGROUND: Adolescent depression varies considerably in its course. However, there remain no biobehavioral predictors of illness trajectory, and follow-up studies in depressed youth are sparse. Here, we sought to examine whether reward function would predict future clinical outcomes in adolescents with depressive symptoms. We utilized the reward flanker fMRI task to assess brain function during distinct reward processes of anticipation, attainment, and positive prediction error (PPE, i.e. receiving uncertain rewards). METHODS: Subjects were 29 psychotropic-medication-free adolescents with mood and anxiety symptoms and 14 healthy controls (HC). All had psychiatric evaluations at baseline and approximately 24-month follow-up. Thirty-two participants (10 HC) had usable fMRI data. Correlation and hierarchical regression models examined baseline symptom severity measures as predictors of follow-up clinical outcomes. Whole-brain analyses examined relationships between neural reward processes and follow-up outcomes. RESULTS: Clinically, anhedonia, but not irritability, predicted future depression and suicidal ideation. Among reward processes, only baseline neural activation during PPE correlated with follow-up depression and anhedonia severity. Specifically, activation in the left angular gyrus-a component of the default mode network-was associated with future depression, while activation in the dorsal anterior cingulate, operculum, and left insula-key salience and pain network regions-was associated with future anhedonia, even when controlling for baseline anhedonia. LIMITATIONS: The small sample size and variable follow-up intervals limit the generalizability of conclusions. CONCLUSIONS: This research suggests that reward dysfunction, indexed by anhedonia, may predict worse clinical trajectories in depressed youth. Adolescents presenting with significant anhedonia should be carefully monitored for illness progression.

Percutaneous Closure of a Giant Aortic Pseudoaneurysm Using Multimodality Imaging Guidance.

Ascending aortic pseudoaneurysm is a rare, life-threatening complication of cardiac surgery. Surgical management is recommended, however, transcatheter techniques offer a less invasive alternative. We describe successful percutaneous closure, guided by using multimodality imaging, in a patient with high surgical risk.

Effect of anomalous pulse timing on call discrimination by females of the gray treefrog (Hyla versicolor): behavioral correlates of neurobiology.

Research has demonstrated that certain midbrain neurons of anurans 'count' interpulse intervals (IPIs). Some neurons fire after exposure to fewer intervals than do others. Counting can be reset to zero if an IPI falls outside the cell's tolerance range. We tested female gray treefrogs for behavioral correlates of these neural response patterns using phonotaxis tests in order to gain a better understanding of the mechanistic bases of female responses to calls. For example, previous work demonstrated females often prefer longer to shorter pulsed advertisement calls, even when the former occur at lower rates. Call attractiveness can also be reduced when pulse duration and timing have been manipulated experimentally or disrupted by acoustic interference. In this study, female responses were consistent with neural data, emphasizing the importance of IPIs. Females discriminated in favor of calls with normal interpulse timing relative to those in which a single IPI was too long or too short. Our data suggest that neural resetting of interval counting by inappropriate intervals may more strongly influence females than reduced firing in response to such intervals on an individual basis. Data also suggest a transition point between 125 ms and 175 ms at which an interval between pulse strings is treated as an interval between calls.

Sound transmission and the recognition of temporally degraded sexual advertisement signals in Cope's gray treefrog (Hyla chrysoscelis).

Acoustic communication signals degrade as they propagate between signalers and receivers. While we generally understand the degrading effects of sound propagation on the structure of acoustic signals, we know considerably less about how receivers make behavioral decisions based on the perception of degraded signals in sonically and structurally complex habitats where communication occurs. In this study of acoustic mate recognition in Cope's gray treefrog, Hyla chrysoscelis (Cope 1880), we investigated how the temporal structure of male advertisement calls was compromised by propagation in a natural habitat and how females responded to stimuli mimicking various levels of temporal degradation. In a sound transmission experiment, we quantified changes in the pulsed structure of signals by broadcasting synthetic calls during active choruses from positions where we typically encountered signalers, and re-recording the signals from positions where we typically encountered potential receivers. Our main finding was that the silent gaps between pulses become increasingly 'filled in' by background noise and reverberations as a function of increasing propagation distance. We also conducted female phonotaxis experiments to determine the threshold modulation depth required to elicit recognition of the pulsatile structure of the call. Females were surprisingly tolerant of degraded temporal structure, and there was a tendency for greater permissiveness at lower playback levels. We discuss these results in terms of presumed mechanisms of call recognition in complex environments and the acoustic adaptation hypothesis.