Cellular kinases incorporated into HIV-1 particles: passive or active passengers?

Phosphorylation is one of the major mechanisms by which the activities of protein factors can be regulated. Such regulation impacts multiple key-functions of mammalian cells, including signal transduction, nucleo-cytoplasmic shuttling, macromolecular complexes assembly, DNA binding and regulation of enzymatic activities to name a few. To ensure their capacities to replicate and propagate efficiently in their hosts, viruses may rely on the phosphorylation of viral proteins to assist diverse steps of their life cycle. It has been known for several decades that particles from diverse virus families contain some protein kinase activity. While large DNA viruses generally encode for viral kinases, RNA viruses and more precisely retroviruses have acquired the capacity to hijack the signaling machinery of the host cell and to embark cellular kinases when budding. Such property was demonstrated for HIV-1 more than a decade ago. This review summarizes the knowledge acquired in the field of HIV-1-associated kinases and discusses their possible function in the retroviral life cycle

Improvements in naturalistic speech-in-noise comprehension in middle-aged and older adults after 3 weeks of computer-based speechreading training

Problems in understanding speech in noisy environments are characteristic for age-related hearing loss. Since hearing aids do not mitigate these communication problems in every case, potential alternatives in a clinical rehabilitation plan need to be explored. This study investigates whether a computer-based speechreading training improves audiovisual speech perception in noise in a sample of middle-aged and older adults (N = 62, 47–83 years) with 32 participants completing a speechreading training and 30 participants of an active control group completing a foreign language training. Before and after training participants performed a speech-in-noise task mimicking real-life communication settings with participants being required to answer a speaker’s questions. Using generalized linear mixed-effects models we found a significant improvement in audiovisual speech perception in noise in the speechreading training group. This is of great relevance as these results highlight the potential of a low-cost and easy-to-implement intervention for a profound and widespread problem as speech-in-noise comprehension impairment

Promoting hearing and cognitive health in audiologic rehabilitation for the well-being of older adults

Objective: With our aging population, an increasing number of older adults with hearing loss have cognitive decline. Hearing care practitioners have an important role in supporting healthy aging and should be knowledgeable about cognitive decline and associated management strategies to maximize successful hearing intervention. Methods: A review of current research and expert opinion. Results: This article outlines the association between hearing loss and cognitive decline/dementia, hypothesized mechanisms underlying this, and considers current research into the effects of hearing intervention on cognitive decline. Cognition into old age, cognitive impairment, dementia, and how to recognize cognitive decline that is not part of normal aging are described. Screening of older asymptomatic adults for cognitive decline and practical suggestions for the delivery of person-centered hearing care are discussed. Holistic management goals, personhood, and person-centered care in hearing care management are considered for older adults with normal cognitive aging through to dementia. A case study illustrates important skills and potential management methods. Prevention strategies for managing hearing and cognitive health and function through to older age, and strategies to maximize successful hearing aid use are provided. Conclusion: This article provides evidence-based recommendations for hearing care professionals supporting older clients to maximize well-being through the cognitive trajectory

HIV-1-associated PKA acts as a cofactor for genome reverse transcription

BACKGROUND: Host cell proteins, including cellular kinases, are embarked into intact HIV-1 particles. We have previously shown that the Cα catalytic subunit of cAMP-dependent protein kinase is packaged within HIV-1 virions as an enzymatically active form able to phosphorylate a synthetic substrate in vitro (Cartier et al. J. Biol. Chem. 278:35211 (2003)). The present study was conceived to investigate the contribution of HIV-1-associated PKA to the retroviral life cycle. RESULTS: NL4.3 viruses were produced from cells cultured in the presence of PKA inhibitors H89 (H89-NL4.3) or Myr-PKI (PKI-NL4.3) and analyzed for viral replication. Despite being mature and normally assembled, and containing expected levels of genomic RNA and RT enzymatic activity, such viruses showed poor infectivity. Indeed, infection generated reduced amounts of strong-strop minus strand DNA, while incoming RNA levels in target cells were unaffected. Decreased cDNA synthesis was also evidenced in intact H89-NL4.3 and PKI-NL4.3 cell free particles using endogenous reverse transcription (ERT) experiments. Moreover, similar defects were reproduced when wild type NL4.3 particles preincubated with PKA inhibitors were subjected to ERT reactions. CONCLUSIONS: Altogether, our results indicate that HIV-1-associated PKA is required for early reverse transcription of the retroviral genome both in cell free intact viruses and in target cells. Accordingly, virus-associated PKA behaves as a cofactor of an intraviral process required for optimal reverse transcription and for early post-entry events

Neural correlates of lexical stress processing in a foreign free-stress language

Introduction The paper examines the discrimination of lexical stress contrasts in a foreign language from a neural perspective. The aim of the study was to identify the areas associated with word stress processing (in comparison with vowel processing), when listeners of a fixed-stress language have to process stress in a foreign free-stress language. Methods We asked French-speaking participants to process stress and vowel contrasts in Spanish, a foreign language that the participants did not know. Participants performed a discrimination task on Spanish word pairs differing either with respect to word stress (penultimate or final stressed word) or with respect to the final vowel while functional magnetic resonance imaging data was acquired. Results Behavioral results showed lower accuracy and longer reaction times for discriminating stress contrasts than vowel contrasts. The contrast Stress > Vowel revealed an increased bilateral activation of regions shown to be associated with stress processing (i.e., supplementary motor area, insula, middle/superior temporal gyrus), as well as a stronger involvement of areas related to more domain-general cognitive control functions (i.e., bilateral inferior frontal gyrus). The contrast Vowel > Stress showed an increased activation in regions typically associated with the default mode network (known for decreasing its activity during attentionally more demanding tasks). Conclusion When processing Spanish stress contrasts as compared to processing vowel contrasts, native listeners of French activated to a higher degree anterior networks including regions related to cognitive control. They also show a decrease in regions related to the default mode network. These findings, together with the behavioral results, reflect the higher cognitive demand, and therefore, the larger difficulties, for French-speaking listeners during stress processing as compared to vowel processing

Ecological Momentary Assessment based Differences between Android and iOS Users of the TrackYourHearing mHealth Crowdsensing Platform

mHealth technologies are increasingly utilized in various medical contexts. Mobile crowdsensing is such a technology, which is often used for data collection scenarios related to questions on chronic disorders. One prominent reason for the latter setting is based on the fact that powerful Ecological Momentary Assessments (EMA) can be performed. Notably, when mobile crowdsensing solutions are used to integrate EMA measurements, many new challenges arise. For example, the measurements must be provided in the same way on different mobile operating systems. However, the newly given possibilities can surpass the challenges. For example, if different mobile operating systems must be technically provided, one direction could be to investigate whether users of different mobile operating systems pose a different behaviour when performing EMA measurements. In a previous work, we investigated differences between iOS and Android users from the TrackYourTinnitus mHealth crowdsensing platform, which has the goal to reveal insights on the daily fluctuations of tinnitus patients. In this work, we investigated differences between iOS and Android users from the TrackYourHearing mHealth crowdsensing platform, which aims at insights on the daily fluctuations of patients with hearing loss. We analyzed 3767 EMA measurements based on a daily applied questionnaire of 84 patients. Statistical analyses have been conducted to see whether these 84 patients differ with respect to the used mobile operating system and their given answers to the EMA measurements. We present the obtained results and compare them to the previous mentioned study. Our insights show the differences in the two studies and that the overall results are worth being investigated in a more indepth manner. Particularly, it must be investigated whether the used mobile operating system constitutes a confounder when gathering EMA-based data through a crowdsensing platform