Auditory motion in the sighted and blind: Early visual deprivation triggers a large-scale imbalance between auditory and “visual” brain regions
Contributors: Giulia Dormal, Mohamed Rezk, Esther Yakobov, Franco Lepore, Olivier Collignon
... How early blindness reorganizes the brain circuitry that supports auditory motion processing remains controversial. We used fMRI to characterize brain responses to in-depth, laterally moving, and static sounds in early blind and sighted individuals. Whole-brain univariate analyses revealed that the right posterior middle temporal gyrus and superior occipital gyrus selectively responded to both in-depth and laterally moving sounds only in the blind. These regions overlapped with regions selective for visual motion (hMT+/V5 and V3A) that were independently localized in the sighted. In the early blind, the right planum temporale showed enhanced functional connectivity with right occipito-temporal regions during auditory motion processing and a concomitant reduced functional connectivity with parietal and frontal regions. Whole-brain searchlight multivariate analyses demonstrated higher auditory motion decoding in the right posterior middle temporal gyrus in the blind compared to the sighted, while decoding accuracy was enhanced in the auditory cortex bilaterally in the sighted compared to the blind. Analyses targeting individually defined visual area hMT+/V5 however indicated that auditory motion information could be reliably decoded within this area even in the sighted group. Taken together, the present findings demonstrate that early visual deprivation triggers a large-scale imbalance between auditory and “visual” brain regions that typically support the processing of motion information.
Contributors: Keith Pardee, Alexander A. Green, Melissa K. Takahashi, Dana Braff, Guillaume Lambert, Jeong Wook Lee, Tom Ferrante, Duo Ma, Nina Donghia, Melina Fan
... The recent Zika virus outbreak highlights the need for low-cost diagnostics that can be rapidly developed for distribution and use in pandemic regions. Here, we report a pipeline for the rapid design, assembly, and validation of cell-free, paper-based sensors for the detection of the Zika virus RNA genome. By linking isothermal RNA amplification to toehold switch RNA sensors, we detect clinically relevant concentrations of Zika virus sequences and demonstrate specificity against closely related Dengue virus sequences. When coupled with a novel CRISPR/Cas9-based module, our sensors can discriminate between viral strains with single-base resolution. We successfully demonstrate a simple, field-ready sample-processing workflow and detect Zika virus from the plasma of a viremic macaque. Our freeze-dried biomolecular platform resolves important practical limitations to the deployment of molecular diagnostics in the field and demonstrates how synthetic biology can be used to develop diagnostic tools for confronting global health crises.
Contributors: Selma Masri, Thales Papagiannakopoulos, Kenichiro Kinouchi, Yu Liu, Marlene Cervantes, Pierre Baldi, Tyler Jacks, Paolo Sassone-Corsi
... The circadian clock controls metabolic and physiological processes through finely tuned molecular mechanisms. The clock is remarkably plastic and adapts to exogenous “zeitgebers,” such as light and nutrition. How a pathological condition in a given tissue influences systemic circadian homeostasis in other tissues remains an unanswered question of conceptual and biomedical importance. Here, we show that lung adenocarcinoma operates as an endogenous reorganizer of circadian metabolism. High-throughput transcriptomics and metabolomics revealed unique signatures of transcripts and metabolites cycling exclusively in livers of tumor-bearing mice. Remarkably, lung cancer has no effect on the core clock but rather reprograms hepatic metabolism through altered pro-inflammatory response via the STAT3-Socs3 pathway. This results in disruption of AKT, AMPK, and SREBP signaling, leading to altered insulin, glucose, and lipid metabolism. Thus, lung adenocarcinoma functions as a potent endogenous circadian organizer (ECO), which rewires the pathophysiological dimension of a distal tissue such as the liver.
Harmonic context influences pitch class equivalence judgments through gestalt and congruency effects
Contributors: Anka Slana, Grega Repovš, W. Tecumseh Fitch, Bruno Gingras
... The context in which a stimulus is presented shapes the way it is processed. This effect has been studied extensively in the field of visual perception. Our understanding of how context affects the processing of auditory stimuli is, however, rather limited. Western music is primarily built on melodies (succession of pitches) typically accompanied by chords (harmonic context), which provides a natural template for the study of context effects in auditory processing. Here, we investigated whether pitch class equivalence judgments of tones are affected by the harmonic context within which the target tones are embedded. Nineteen musicians and 19 non-musicians completed a change detection task in which they were asked to determine whether two successively presented target tones, heard either in isolation or with a chordal accompaniment (same or different chords), belonged to the same pitch class. Both musicians and non-musicians were most accurate when the chords remained the same, less so in the absence of chordal accompaniment, and least when the chords differed between both target tones. Further analysis investigating possible mechanisms underpinning these effects of harmonic context on task performance revealed that both a change in gestalt (change in either chord or pitch class), as well as incongruency between change in target tone pitch class and change in chords, led to reduced accuracy and longer reaction times. Our results demonstrate that, similarly to visual processing, auditory processing is influenced by gestalt and congruency effects.
Contributors: Romain Banchereau, Seunghee Hong, Brandi Cantarel, Nicole Baldwin, Jeanine Baisch, Michelle Edens, Alma-Martina Cepika, Peter Acs, Jacob Turner, Esperanza Anguiano
... Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to nucleic acids and highly diverse clinical manifestations. To assess its molecular heterogeneity, we longitudinally profiled the blood transcriptome of 158 pediatric patients. Using mixed models accounting for repeated measurements, demographics, treatment, disease activity (DA), and nephritis class, we confirmed a prevalent IFN signature and identified a plasmablast signature as the most robust biomarker of DA. We detected gradual enrichment of neutrophil transcripts during progression to active nephritis and distinct signatures in response to treatment in different nephritis subclasses. Importantly, personalized immunomonitoring uncovered individual correlates of disease activity that enabled patient stratification into seven groups, supported by patient genotypes. Our study uncovers the molecular heterogeneity of SLE and provides an explanation for the failure of clinical trials. This approach may improve trial design and implementation of tailored therapies in genetically and clinically complex autoimmune diseases.
Contributors: Mónica Padilla de la Torre, Elodie F. Briefer, Brad M. Ochocki, Alan G. McElligott, Tom Reader
... Individual recognition in gregarious species is fundamental in order to avoid misdirected parental investment. In ungulates, two very different parental care strategies have been identified: ‘hider’ offspring usually lie concealed in vegetation whereas offspring of ‘follower’ species remain with their mothers while they forage. These two strategies have been suggested to impact on mother–offspring vocal recognition, with unidirectional recognition of the mother by offspring occurring in hiders and bidirectional recognition in followers. In domestic cattle, Bos taurus, a facultative hider species, vocal communication and recognition have not been studied in detail under free-ranging conditions, where cows and calves can graze freely and where hiding behaviour can occur. We hypothesized that, as a hider species, cattle under these circumstances would display unidirectional vocal recognition. To test this hypothesis, we conducted playback experiments using mother–offspring contact calls. We found that cows were more likely to respond, by moving their ears and/or looking, turning or walking towards the loudspeaker, to calls of their own calves than to calls from other calves. Similarly, calves responded more rapidly, and were more likely to move their ears and/or look, turn or walk towards the loudspeaker, and to call back and/or meet their mothers, in response to calls from their own mothers than to calls from other females. Contrary to our predictions, our results suggest that mother–offspring vocal individual recognition is bidirectional in cattle. Additionally, mothers of younger calves tended to respond more strongly to playbacks than mothers of older calves. Therefore, mother responses to calf vocalizations are at least partially influenced by calf age.
Articles - Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis
Contributors: Eric M Thompson, Thomas Hielscher, Eric Bouffet, Marc Remke, Betty Luu, Sridharan Gururangan, Roger E McLendon, Darell D Bigner, Eric S Lipp, Sebastien Perreault
... Patients with incomplete surgical resection of medulloblastoma are controversially regarded as having a marker of high-risk disease, which leads to patients undergoing aggressive surgical resections, so-called second-look surgeries, and intensified chemoradiotherapy. All previous studies assessing the clinical importance of extent of resection have not accounted for molecular subgroup. We analysed the prognostic value of extent of resection in a subgroup-specific manner.
Contributors: Keith B. Hengen, Alejandro Torrado Pacheco, James N. McGregor, Stephen D. Van Hooser, Gina G. Turrigiano
... Homeostatic mechanisms stabilize neural circuit function by keeping firing rates within a set-point range, but whether this process is gated by brain state is unknown. Here, we monitored firing rate homeostasis in individual visual cortical neurons in freely behaving rats as they cycled between sleep and wake states. When neuronal firing rates were perturbed by visual deprivation, they gradually returned to a precise, cell-autonomous set point during periods of active wake, with lengthening of the wake period enhancing firing rate rebound. Unexpectedly, this resetting of neuronal firing was suppressed during sleep. This raises the possibility that memory consolidation or other sleep-dependent processes are vulnerable to interference from homeostatic plasticity mechanisms.
Articles - Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto—GBG 69): a randomised, phase 3 trial
Contributors: Michael Untch, Christian Jackisch, Andreas Schneeweiss, Bettina Conrad, Bahriye Aktas, Carsten Denkert, Holger Eidtmann, Hermann Wiebringhaus, Sherko Kümmel, Jörn Hilfrich
... In metastatic breast cancer, nab-paclitaxel has been shown to significantly increase progression-free survival compared with solvent-based paclitaxel. The GeparSepto (GBG 69) trial assessed whether weekly nab-paclitaxel could increase the proportion of patients achieving pathological complete response compared with weekly solvent-based paclitaxel, both followed by epirubicin plus cyclophosphamide as neoadjuvant treatment.
Laser-evoked cortical responses in freely-moving rats reflect the activation of C-fibre afferent pathways
Contributors: X.L. Xia, W.W. Peng, G.D. Iannetti, L. Hu
... The limited success of translating basic animal findings into effective clinical treatments of pain can be partly ascribed to the use of sub-optimal models. Murine models of pain often consist in recording (1) threshold responses (like the tail-flick reflex) elicited by (2) non-nociceptive specific inputs in (3) anaesthetized animals. The direct cortical recording of laser-evoked potentials (LEPs) elicited by stimuli of graded energies in freely-moving rodents avoids these three important pitfalls, and has thus the potential of improving such translation. Murine LEPs are classically reported to consist of two distinct components, reflecting the activity of Aδ- and C-fibre afferent pathways. However, we have recently demonstrated that the so-called “Aδ-LEPs” in fact reflect the activation of the auditory system by laser-generated ultrasounds. Here we used ongoing white noise to avoid the confound represented by the early auditory response, and thereby comprehensively characterized the physiological properties of C-fibre LEPs recorded directly from the exposed surface of the rat brain. Stimulus–response functions indicated that response amplitude is positively related to the stimulus energy, as well as to nocifensive behavioral score. When displayed using average reference, murine LEPs consist of three distinct deflections, whose polarity, order, and topography are surprisingly similar to human LEPs. The scalp topography of the early N1 wave is somatotopically-organized, likely reflecting the activity of the primary somatosensory cortex, while topographies of the later N2 and P2 waves are more centrally distributed. These results indicate that recording LEPs in freely-moving rats is a valid model to improve the translation of animal results to human physiology and pathophysiology.