The phagophore in four dimensions-a study in wood.

One of the key features of macroautophagy/autophagy is the dynamic nature of the membrane rearrangements that take place during expansion of the phagophore, the sequestering compartment that matures into an autophagosome. There are various ways to depict this process, but in most cases the method ultimately relies on a two-dimensional medium. Most people working in the field of autophagy realize that the typical 'C'-shaped drawing of a phagophore is meant to represent a cup- or bowl-like structure that exists in the cell in 3 dimensions. However, explaining this concept to a lay person often leads to confusion and misinterpretation. Accordingly, we decided to generate a four-dimensional version of the expanding phagophore as a wood sculpture, that depicts this transient compartment in 3 dimensions over time. ABBREVIATIONS: ER: endoplasmic reticulum.

Annotated Draft Genome Assemblies for the Northern Bobwhite (Colinus virginianus) and the Scaled Quail (Callipepla squamata) Reveal Disparate Estimates of Modern Genome Diversity and Historic Effective Population Size.

Northern bobwhite (Colinus virginianus; hereafter bobwhite) and scaled quail (Callipepla squamata) populations have suffered precipitous declines across most of their US ranges. Illumina-based first- (v1.0) and second- (v2.0) generation draft genome assemblies for the scaled quail and the bobwhite produced N50 scaffold sizes of 1.035 and 2.042 Mb, thereby producing a 45-fold improvement in contiguity over the existing bobwhite assembly, and ≥90% of the assembled genomes were captured within 1313 and 8990 scaffolds, respectively. The scaled quail assembly (v1.0 = 1.045 Gb) was ∼20% smaller than the bobwhite (v2.0 = 1.254 Gb), which was supported by kmer-based estimates of genome size. Nevertheless, estimates of GC content (41.72%; 42.66%), genome-wide repetitive content (10.40%; 10.43%), and MAKER-predicted protein coding genes (17,131; 17,165) were similar for the scaled quail (v1.0) and bobwhite (v2.0) assemblies, respectively. BUSCO analyses utilizing 3023 single-copy orthologs revealed a high level of assembly completeness for the scaled quail (v1.0; 84.8%) and the bobwhite (v2.0; 82.5%), as verified by comparison with well-established avian genomes. We also detected 273 putative segmental duplications in the scaled quail genome (v1.0), and 711 in the bobwhite genome (v2.0), including some that were shared among both species. Autosomal variant prediction revealed ∼2.48 and 4.17 heterozygous variants per kilobase within the scaled quail (v1.0) and bobwhite (v2.0) genomes, respectively, and estimates of historic effective population size were uniformly higher for the bobwhite across all time points in a coalescent model. However, large-scale declines were predicted for both species beginning ∼15-20 KYA.

Diagnosing mild traumatic brain injury: where are we now?

BACKGROUND: The brain acoustic monitor (BAM), an indicator of cerebral autoregulation, has previously shown high sensitivity but low specificity for computed tomographic (CT) abnormality in patients following the clinical diagnosis of traumatic brain injury. We assessed the utility of the BAM in diagnosing mild TBI (mTBI) in patients with and without normal findings of CT scan, a population for which there are a few objective markers of disease. METHODS: We prospectively studied 369 patients with mechanism of injury consistent with TBI. The diagnosis was evaluated by five methods: (a) study enrollment (i.e., mechanism of injury), (b) signs of head trauma, (c) expert physician assessment, (d) presence of initial symptoms (loss of consciousness [LOC]; amnesia), and (e) BAM. All patients had a head CT scan. We compared the BAM screen results with the diagnosis of mTBI and BAM data from 50 normal volunteers and 49 trauma control patients not thought to have TBI. RESULTS: None of the diagnostic methods correlated well with the others. Correlation between the methods ranged from 21% to 71%. BAM discriminated between patients with mTBI versus without TBI (p<0.01) and patients with mTBI versus normal subjects (p<0.001). There were 14 patients with new abnormal findings of CT scans. A history of LOC and physical signs of head injury were associated with a new abnormality on head CT (p<0.05 and p<0.01, respectively), whereas an abnormal BAM signal was suggestive (p=0.08). The sensitivity of BAM abnormality for head CT abnormality was 100%, with a specificity of 30.14%. CONCLUSION: There is no gold standard for the diagnosis of mTBI. BAM screening is a useful diagnostic adjunct in patients with mTBI and may facilitate decision making. An abnormal BAM reading adds significance to LOC as a predictor of a new abnormality on head CT. In our study, opting not to CT scan patients with a normal BAM signal would have missed no new CT findings and no patients who required medical intervention for TBI, at a cost savings of $202,950.

A noninvasive portable acoustic diagnostic system to differentiate ischemic from hemorrhagic stroke.

PURPOSE: To determine if a noninvasive brain acoustic monitor can differentiate acoustic responses from "normal patients" and ischemic from hemorrhagic stroke patients. METHODS: A laptop-sized passive acoustic monitoring system acquires arterial-pressure-generated signals during a 15-second monitoring session from sensors placed at the radial artery and on the fore-head. The arterial pulse waveform from the head is compared with that of the arterial waveform to generate the time-domain signal comparison. Frequency domain signals from each area are also compared. The study involved patients with diagnosis of first stroke who could be monitored within 12 hours of symptom onset and normal subjects who provided informed consent. Individuals with history of brain injury, stroke, or other brain disease were excluded. RESULTS: Twelve normal subjects and 6 ischemic stroke, 2 transient ischemic attack (TIA), and 3 hemorrhagic stroke patients were monitored. Frequency response analysis identified uniform frequency responses in normal subjects. The signal in ischemic stroke patients was characterized by a divergence of the radial and cranial frequency response between 10 and 50 Hz of 10 dB or greater. In intracerebral hemorrhage patients, a divergence was seen below 10 Hz but not in the band above 10 Hz. TIA patients were monitored after symptom resolution and showed a divergence <10 dB in both bands, similar to normal subjects. CONCLUSIONS: In a pilot study using a noninvasive monitor, the authors detected a potential to differentiate between normal subjects and those with cerebral ischemia or hemorrhage.

Preliminary trial of a noninvasive brain acoustic monitor in trauma patients with severe closed head injury.

BACKGROUND: There is no simple way to assess the injured patient after a loss of consciousness. Computed tomographic scanning is required to rule out anatomic injuries, and invasive intracranial pressure monitoring is needed for the patient with severe traumatic brain injury (TBI). We hypothesized that a noninvasive acoustic monitoring system could provide useful clinical data on the severity and progression of TBI. METHODS: Twenty-eight consecutive patients with severe TBI and an indication for invasive intracranial pressure monitoring were studied using the Brain Acoustic Monitor (BAM). Monitoring occurred for 1- to 3-hour time periods on the day of enrollment and each day until the patient's condition stabilized. BAM signals were categorized on the basis of amplitude and positive-to-negative deflection ratio, and then compared with the patient's clinical outcome. RESULTS: BAM signal correlated very strongly with clinical outcome: in 27 of 29 sessions with a normal signal, patients were discharged at a Glasgow Coma Scale score > 13, whereas in 36 of 42 sessions with an abnormal signal, the patient either died or left the hospital with a Glasgow Coma Scale score < 9 (p < 0.00001). The correlation between clinical outcome and initial BAM reading was even stronger: 10 of 10 patients with a normal signal did well, as compared with 3 of 18 patients with an abnormal signal. CONCLUSION: Noninvasive monitoring of the injured brain can discriminate those patients who will have a poor clinical outcome from those who will do well. Further trials of the BAM are indicated.