In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies.

BACKGROUND: The rapid and continual viral escape from neutralizing antibodies is well documented in HIV-1 infection. Here we report in vivo emergence of viruses with heightened sensitivity to neutralizing antibodies, sometimes paralleling the development of neutralization escape. METHODOLOGY/PRINCIPAL FINDINGS: Sequential viral envs were amplified from seven HIV-1 infected men monitored from seroconversion up to 5 years after infection. Env-recombinant infectious molecular clones were generated and tested for coreceptor use, macrophage tropism and neutralization sensitivity to homologous and heterologous serum, soluble CD4 and monoclonal antibodies IgG1b12, 2G12 and 17b. We found that HIV-1 evolves sensitivity to contemporaneous neutralizing antibodies during infection. Neutralization sensitive viruses grow out even when potent autologous neutralizing antibodies are present in patient serum. Increased sensitivity to neutralization was associated with susceptibility of the CD4 binding site or epitopes induced after CD4 binding, and mediated by complex envelope determinants including V3 and V4 residues. The development of neutralization sensitive viruses occurred without clinical progression, coreceptor switch or change in tropism for primary macrophages. CONCLUSIONS: We propose that an interplay of selective forces for greater virus replication efficiency without the need to resist neutralizing antibodies in a compartment protected from immune surveillance may explain the temporal course described here for the in vivo emergence of HIV-1 isolates with high sensitivity to neutralizing antibodies

Transmission Characteristics of Primate Vocalizations: Implications for Acoustic Analyses

Acoustic analyses have become a staple method in field studies of animal vocal communication, with nearly all investigations using computer-based approaches to extract specific features from sounds. Various algorithms can be used to extract acoustic variables that may then be related to variables such as individual identity, context or reproductive state. Habitat structure and recording conditions, however, have strong effects on the acoustic structure of sound signals. The purpose of this study was to identify which acoustic parameters reliably describe features of propagated sounds. We conducted broadcast experiments and examined the influence of habitat type, transmission height, and re-recording distance on the validity (deviation from the original sound) and reliability (variation within identical recording conditions) of acoustic features of different primate call types. Validity and reliability varied independently of each other in relation to habitat, transmission height, and re-recording distance, and depended strongly on the call type. The smallest deviations from the original sounds were obtained by a visually-controlled calculation of the fundamental frequency. Start- and end parameters of a sound were most susceptible to degradation in the environment. Because the recording conditions can have appreciable effects on acoustic parameters, it is advisable to validate the extraction method of acoustic variables from recordings over longer distances before using them in acoustic analyses

Percutaneous Coronary Intervention Versus Medical Therapy for Chronic Total Occlusion of Coronary Arteries:A Systematic Review and Meta-Analysis

PURPOSE OF REVIEW: Chronic total occlusion (CTO) of the coronary arteries is a significant clinical problem and has traditionally been treated by medical therapy or coronary artery bypass grafting. Recent studies have examined percutaneous coronary intervention (PCI) as an alternative option. RECENT FINDINGS: This systematic review and meta-analysis compared medical therapy to PCI for treating CTOs. PubMed and Embase were searched from their inception to March 2019 for studies that compared medical therapy and PCI for clinical outcomes in patients with CTOs. Quality of the included studies was assessed by Newcastle-Ottawa scale. The results were pooled by DerSimonian and Laird random- or fixed-effect models as appropriate. Heterogeneity between studies and publication bias was evaluated by I2 index and Egger's regression, respectively. Of the 703 entries screened, 17 studies were included in the final analysis. This comprised 11,493 participants. Compared to PCI, medical therapy including randomized and observational studies was significantly associated with higher risk of all-cause mortality (risk ratio (RR) 1.99, 95% CI 1.38-2.86), cardiac mortality (RR 2.36 (1.97-2.84)), and major adverse cardiac event (RR 1.25 (1.03-1.51)). However, no difference in the rate of myocardial infarction and repeat revascularization procedures was observed between the two groups. Univariate meta-regression demonstrated multiple covariates as independent moderating factors for myocardial infarction and repeat revascularization but not cardiac death and all-cause mortality. However, when only randomized studies were included, there was no difference in overall mortality or cardiac death. In CTO, when considering randomized and observational studies, medical therapy might be associated with a higher risk of mortality and myocardial infarction compared to PCI treatment

The potential to encode sex, age, and individual identity in the alarm calls of three species of Marmotinae

In addition to encoding referential information and information about the sender’s motivation, mammalian alarm calls may encode information about other attributes of the sender, providing the potential for recognition among kin, mates, and neighbors. Here, we examined 96 speckled ground squirrels (Spermophilus suslicus), 100 yellow ground squirrels (Spermophilus fulvus) and 85 yellow-bellied marmots (Marmota flaviventris) to determine whether their alarm calls differed between species in their ability to encode information about the caller’s sex, age, and identity. Alarm calls were elicited by approaching individually identified animals in live-traps. We assume this experimental design modeled a naturally occurring predatory event, when receivers should acquire information about attributes of a caller from a single bout of alarm calls. In each species, variation that allows identification of the caller’s identity was greater than variation allowing identification of age or sex. We discuss these results in relation to each species’ biology and sociality

Call Cultures in Orang-Utans?

BACKGROUND: Several studies suggested great ape cultures, arguing that human cumulative culture presumably evolved from such a foundation. These focused on conspicuous behaviours, and showed rich geographic variation, which could not be attributed to known ecological or genetic differences. Although geographic variation within call types (accents) has previously been reported for orang-utans and other primate species, we examine geographic variation in the presence/absence of discrete call types (dialects). Because orang-utans have been shown to have geographic variation that is not completely explicable by genetic or ecological factors we hypothesized that this will be similar in the call domain and predict that discrete call type variation between populations will be found. METHODOLOGY/PRINCIPAL FINDINGS: We examined long-term behavioural data from five orang-utan populations and collected fecal samples for genetic analyses. We show that there is geographic variation in the presence of discrete types of calls. In exactly the same behavioural context (nest building and infant retrieval), individuals in different wild populations customarily emit either qualitatively different calls or calls in some but not in others. By comparing patterns in call-type and genetic similarity, we suggest that the observed variation is not likely to be explained by genetic or ecological differences. CONCLUSION/SIGNIFICANCE: These results are consistent with the potential presence of 'call cultures' and suggest that wild orang-utans possess the ability to invent arbitrary calls, which spread through social learning. These findings differ substantially from those that have been reported for primates before. First, the results reported here are on dialect and not on accent. Second, this study presents cases of production learning whereas most primate studies on vocal learning were cases of contextual learning. We conclude with speculating on how these findings might assist in bridging the gap between vocal communication in non-human primates and human speech

Anesthesia advanced circulatory life support

The constellation of advanced cardiac life support (ACLS) events, such as gas embolism, local anesthetic overdose, and spinal bradycardia, in the perioperative setting differs from events in the pre-hospital arena. As a result, modification of traditional ACLS protocols allows for more specific etiology-based resuscitation. Perioperative arrests are both uncommon and heterogeneous and have not been described or studied to the same extent as cardiac arrest in the community. These crises are usually witnessed, frequently anticipated, and involve a rescuer physician with knowledge of the patient's comorbidities and coexisting anesthetic or surgically related pathophysiology. When the health care provider identifies the probable cause of arrest, the practitioner has the ability to initiate medical management rapidly. Recommendations for management must be predicated on expert opinion and physiological understanding rather than on the standards currently being used in the generation of ACLS protocols in the community. Adapting ACLS algorithms and considering the differential diagnoses of these perioperative events may prevent cardiac arrest

Neural processing of natural sounds

Natural sounds include animal vocalizations, environmental sounds such as wind, water and fire noises and non-vocal sounds made by animals and humans for communication. These natural sounds have characteristic statistical properties that make them perceptually salient and that drive auditory neurons in optimal regimes for information transmission.Recent advances in statistics and computer sciences have allowed neuro-physiologists to extract the stimulus-response function of complex auditory neurons from responses to natural sounds. These studies have shown a hierarchical processing that leads to the neural detection of progressively more complex natural sound features and have demonstrated the importance of the acoustical and behavioral contexts for the neural responses.High-level auditory neurons have shown to be exquisitely selective for conspecific calls. This fine selectivity could play an important role for species recognition, for vocal learning in songbirds and, in the case of the bats, for the processing of the sounds used in echolocation. Research that investigates how communication sounds are categorized into behaviorally meaningful groups (e.g. call types in animals, words in human speech) remains in its infancy.Animals and humans also excel at separating communication sounds from each other and from background noise. Neurons that detect communication calls in noise have been found but the neural computations involved in sound source separation and natural auditory scene analysis remain overall poorly understood. Thus, future auditory research will have to focus not only on how natural sounds are processed by the auditory system but also on the computations that allow for this processing to occur in natural listening situations.The complexity of the computations needed in the natural hearing task might require a high-dimensional representation provided by ensemble of neurons and the use of natural sounds might be the best solution for understanding the ensemble neural code

A gestural repertoire of 1-2year old human children : in search of the ape gestures

This project was made possible with the generous financial help of the Baverstock Bequest to the Psychology and Neuroscience Department at the University of St Andrews.When we compare human gestures to those of other apes, it looks at first like there is nothing much to compare at all. In adult humans, gestures are thought to be a window into the thought processes accompanying language, and sign languages are equal to spoken language with all of its features. While some research firmly emphasises the difference between human gestures and those of other apes, the question about whether there are any commonalities has rarely been investigated, and is mostly confined to pointing gestures. The gestural repertoires of nonhuman ape species have been carefully studied and described with regard to their form and function – but similar approaches are much rarer in the study of human gestures. This paper applies the methodology commonly used in the study of nonhuman ape gestures to the gestural communication of human children in their second year of life. We recorded (n=13) children’s gestures in a natural setting with peers and caregivers in Germany and Uganda. Children employed 52 distinct gestures, 46 (89%) of which are present in the chimpanzee repertoire. Like chimpanzees, they used them both singly, and in sequences; and employed individual gestures flexibly towards different goals.Publisher PDFPeer reviewe