Research into induced pluripotent stem cells (iPSCs) has expanded at a remarkable pace in the decade since Shinya Yamanaka and Kazutoshi Takahashi first reported their groundbreaking discovery in 2006. This Timeline highlights the key events in the development of this field, including basic insights into the production of iPSCs and how they have been applied to improve our understanding and treatment of human disease.
Contributors:Matthew W. Snyder, Martin Kircher, Andrew J. Hill, Riza M. Daza, Jay Shendure
Nucleosome positioning varies between cell types. By deep sequencing cell-free DNA (cfDNA), isolated from circulating blood plasma, we generated maps of genome-wide in vivo nucleosome occupancy and found that short cfDNA fragments harbor footprints of transcription factors. The cfDNA nucleosome occupancies correlate well with the nuclear architecture, gene structure, and expression observed in cells, suggesting that they could inform the cell type of origin. Nucleosome spacing inferred from cfDNA in healthy individuals correlates most strongly with epigenetic features of lymphoid and myeloid cells, consistent with hematopoietic cell death as the normal source of cfDNA. We build on this observation to show how nucleosome footprints can be used to infer cell types contributing to cfDNA in pathological states such as cancer. Since this strategy does not rely on genetic differences to distinguish between contributing tissues, it may enable the noninvasive monitoring of a much broader set of clinical conditions than currently possible.
Speech recognition is rapid, automatic and amazingly robust. How the brain is able to decode speech from noisy acoustic inputs is unknown. We show that the brain recognizes speech by integrating bottom-up acoustic signals with top-down predictions.
The central role of the microbiome in critical illness is supported by a half century of experimental and clinical study. The physiological effects of critical illness and the clinical interventions of intensive care substantially alter the microbiome. In turn, the microbiome predicts patients' susceptibility to disease, and manipulation of the microbiome has prevented or modulated critical illness in animal models and clinical trials. This Review surveys the microbial ecology of critically ill patients, presents the facts and unanswered questions surrounding gut-derived sepsis, and explores the radically altered ecosystem of the injured alveolus. The revolution in culture-independent microbiology has provided the tools needed to target the microbiome rationally for the prevention and treatment of critical illness, holding great promise to improve the acute and chronic outcomes of the critically ill.
China is experiencing growing epidemics of HIV and sexually transmitted infections (STIs). Programmes to train physicians in China on HIV and STI knowledge, diagnosis, treatment, and risk reduction counselling can potentially reduce HIV and STI risk among high-risk patients. We aimed to assess a knowledge-based and skills-based programme for physicians in China to reduce patients' STI risk.
Contributors:Juan Sebastian Ulloa, Amandine Gasc, Phillipe Gaucher, Thierry Aubin, Maxime Réjou-Méchain, Jérôme Sueur
Acoustic monitoring has proved to be an efficient approach to monitor wildlife, notably in environments with limited visibility, such as tropical rainforests. Today, recording equipment allows acoustic data to be gathered in remote areas at wide spatial and temporal scales. The resulting datasets are large and the use of automated processing systems to extract relevant information can greatly facilitate their analysis. Here, we have developed signal processing techniques to reveal the spatio-temporal dynamics of an emblematic bird voice of the neotropical forest: the song of the Screaming Piha (Lipaugus vociferans). Using recordings made in a French Guianan lowland forest, with an array of 24 microphones in a three dimensional space, we implemented a detection system based on spectrogram cross-correlation to trace the vocalisations of L. vociferans. We tuned the detection system based on the percentage area under the Receiver Operating Characteristic curve, finding a maximum of 95.88%. To strictly minimise false positives, we set the operating point to have 34.9% true positives and 0% false positives. We detected a total of 12,735 songs attributed to the study bird during 25 study days. We found that spatial patterns of lower activity corresponded to a zone having smaller trees and more tree gaps — a known liana forest patch — suggesting that Screaming Piha birds tend to avoid non-mature primary forests. The sampling sites near the creeks had more detections than the sites further away, suggesting that the lek mating arenas might be distributed strategically to be near to a source of water. We also found a marked temporal pattern. The lek was active during the whole day, from sunrise to sunset, with two peaks of activity shifted by more than 2h from the dawn and dusk chorus. The approach described here can be tested using other conspicuous and stereotyped sounds that occur within a heterogeneous and noisy background. To decipher the complex interacting sounds of the tropical forest, these focal studies on specific acoustic elements should be complemented with community or soundscape analysis, to demonstrate the human impact on the ecosystem and to provide guidelines for natural resource management.
Contributors:Paulo Barraza, Mario Chavez, Eugenio Rodríguez
Similar to linguistic stimuli, music can also prime the meaning of a subsequent word. However, it is so far unknown what is the brain dynamics underlying the semantic priming effect induced by music, and its relation to language. To elucidate these issues, we compare the brain oscillatory response to visual words that have been semantically primed either by a musical excerpt or by an auditory sentence. We found that semantic violation between music–word pairs triggers a classical ERP N400, and induces a sustained increase of long-distance theta phase synchrony, along with a transient increase of local gamma activity. Similar results were observed after linguistic semantic violation except for gamma activity, which increased after semantic congruence between sentence–word pairs. Our findings indicate that local gamma activity is a neural marker that signals different ways of semantic processing between music and language, revealing the dynamic and self-organized nature of the semantic processing.