On the mechanism of response latencies in auditory nerve fibers

Despite the structural differences of the middle and inner ears, the latency pattern in auditory nerve fibers to an identical sound has been found similar across numerous species. Studies have shown the similarity in remarkable species with distinct cochleae or even without a basilar membrane. This stimulus-, neuron-, and species- independent similarity of latency cannot be simply explained by the concept of cochlear traveling waves that is generally accepted as the main cause of the neural latency pattern. An original concept of Fourier pattern is defined, intended to characterize a feature of temporal processing—specifically phase encoding—that is not readily apparent in more conventional analyses. The pattern is created by marking the first amplitude maximum for each sinusoid component of the stimulus, to encode phase information. The hypothesis is that the hearing organ serves as a running analyzer whose output reflects synchronization of auditory neural activity consistent with the Fourier pattern. A combined research of experimental, correlational and meta-analysis approaches is used to test the hypothesis. Manipulations included phase encoding and stimuli to test their effects on the predicted latency pattern. Animal studies in the literature using the same stimulus were then compared to determine the degree of relationship. The results show that each marking accounts for a large percentage of a corresponding peak latency in the peristimulus-time histogram. For each of the stimuli considered, the latency predicted by the Fourier pattern is highly correlated with the observed latency in the auditory nerve fiber of representative species. The results suggest that the hearing organ analyzes not only amplitude spectrum but also phase information in Fourier analysis, to distribute the specific spikes among auditory nerve fibers and within a single unit. This phase-encoding mechanism in Fourier analysis is proposed to be the common mechanism that, in the face of species differences in peripheral auditory hardware, accounts for the considerable similarities across species in their latency-by-frequency functions, in turn assuring optimal phase encoding across species. Also, the mechanism has the potential to improve phase encoding of cochlear implants

BUMC Annual Report

Annual report of the Boston University Medical Center

Annual Progress Report, Study of Dynamic Rigidity of Marine Sediments

The report is divided into two tasks with each task summary being prepared by the principal investigators of that task. Task 1 includes a study of the dynamic rigidity, acoustic, and other engineering properties of marine sediments. Task 2 covers a study of upper ocean turbulence as related to acoustic measurements. (Author)http://archive.org/details/studyofdynamicri00and

Investigating the relationship between mitochondrial genetic variation and cardiovascular-related traits to develop a framework for mitochondrial phenome-wide association studies

BACKGROUND: Mitochondria play a critical role in the cell and have DNA independent of the nuclear genome. There is much evidence that mitochondrial DNA (mtDNA) variation plays a role in human health and disease, however, this area of investigation has lagged behind research into the role of nuclear genetic variation on complex traits and phenotypic outcomes. Phenome-wide association studies (PheWAS) investigate the association between a wide range of traits and genetic variation. To date, this approach has not been used to investigate the relationship between mtDNA variants and phenotypic variation. Herein, we describe the development of a PheWAS framework for mtDNA variants (mt-PheWAS). Using the Metabochip custom genotyping array, nuclear and mitochondrial DNA variants were genotyped in 11,519 African Americans from the Vanderbilt University biorepository, BioVU. We employed both polygenic modeling and association testing with mitochondrial single nucleotide polymorphisms (mtSNPs) to explore the relationship between mtDNA variants and a group of eight cardiovascular-related traits obtained from de-identified electronic medical records within BioVU. RESULTS: Using polygenic modeling we found evidence for an effect of mtDNA variation on total cholesterol and type 2 diabetes (T2D). After performing comprehensive mitochondrial single SNP associations, we identified an increased number of single mtSNP associations with total cholesterol and T2D compared to the other phenotypes examined, which did not have more significantly associated SNPs than would be expected by chance. Among the mtSNPs significantly associated with T2D we identified variant mt16189, an association previously reported only in Asian and European-descent populations. CONCLUSIONS: Our replication of previous findings and identification of novel associations from this initial study suggest that our mt-PheWAS approach is robust for investigating the relationship between mitochondrial genetic variation and a range of phenotypes, providing a framework for future mt-PheWAS

BUMC Annual Report

Annual report of the Boston University Medical Center

EARLY RESULTS OF ECOPOESIS EXPERIMENTS IN THE SHOT MARTIAN ENVIRONMENT SIMULATOR

ABSTRACT Humanity is on the verge of having the capability of constructively directing environmental changes on a planetary scale. One could argue that we are making these changes on Earth today, but in a negative manner. Within the foreseeable future, we will have the technology to modify Mars' environment, and make it a habitable planet. However, we do not have enough information to determine the course of such an event. SHOT has designed and built a test-bed apparatus that can replicate most of Mars' environment conditions (with the notable exceptions of gravity and cosmic radiation) within a 5.6 liter chamber. Here, we present the results of initial experiments to determine the suitability of specific microorganisms as pioneering life-forms for Mars. Included among the potential pioneers were five genera of cyanobacteria (Anabaena, Chroococcidiopsis, Plectonema, Synechococcus and Syenechocystis), and three partially-characterized eubacterial strains that were isolated from Chile's Atacama Desert (two species of Bacillus and Klebsiella oxytoca). During these initial trials, we used a present-day mix of martian atmsospheric gases, but at a pressure of 100 mbar (10 times Mars's current atmospheric pressure). Organisms were inoculated into samples of JSC Mars-1 soil stimulant and exposed to full-spectrum simulated martian sunlight. Day/night temperature cycled from 26°C to -80°C and back. Experiments included a 24-hour, brief-exposure trial, a 7-day trial, a14-day trial and a 5-week trial to determine the survival and growth of our potential martian pioneers

Re-visiting Meltsner: Policy Advice Systems and the Multi-Dimensional Nature of Professional Policy Analysis

10.2139/ssrn.15462511-2

Age-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade

Age-associated B cells (ABC) accumulate with age and in individuals with different immunological disorders, including cancer patients treated with immune checkpoint blockade and those with inborn errors of immunity. Here, we investigate whether ABCs from different conditions are similar and how they impact the longitudinal level of the COVID-19 vaccine response. Single-cell RNA sequencing indicates that ABCs with distinct aetiologies have common transcriptional profiles and can be categorised according to their expression of immune genes, such as the autoimmune regulator (AIRE). Furthermore, higher baseline ABC frequency correlates with decreased levels of antigen-specific memory B cells and reduced neutralising capacity against SARS-CoV-2. ABCs express high levels of the inhibitory FcγRIIB receptor and are distinctive in their ability to bind immune complexes, which could contribute to diminish vaccine responses either directly, or indirectly via enhanced clearance of immune complexed-antigen. Expansion of ABCs may, therefore, serve as a biomarker identifying individuals at risk of suboptimal responses to vaccination