The sense of touch provides critical information about our physical environment by transforming mechanical energy into electrical signals. It is postulated that mechanically activated cation channels ...initiate touch sensation, but the identity of these molecules in mammals has been elusive. Piezo2 is a rapidly adapting, mechanically activated ion channel expressed in a subset of sensory neurons of the dorsal root ganglion and in cutaneous mechanoreceptors known as Merkel-cell-neurite complexes. It has been demonstrated that Merkel cells have a role in vertebrate mechanosensation using Piezo2, particularly in shaping the type of current sent by the innervating sensory neuron; however, major aspects of touch sensation remain intact without Merkel cell activity. Here we show that mice lacking Piezo2 in both adult sensory neurons and Merkel cells exhibit a profound loss of touch sensation. We precisely localize Piezo2 to the peripheral endings of a broad range of low-threshold mechanoreceptors that innervate both hairy and glabrous skin. Most rapidly adapting, mechanically activated currents in dorsal root ganglion neuronal cultures are absent in Piezo2 conditional knockout mice, and ex vivo skin nerve preparation studies show that the mechanosensitivity of low-threshold mechanoreceptors strongly depends on Piezo2. This cellular phenotype correlates with an unprecedented behavioural phenotype: an almost complete deficit in light-touch sensation in multiple behavioural assays, without affecting other somatosensory functions. Our results highlight that a single ion channel that displays rapidly adapting, mechanically activated currents in vitro is responsible for the mechanosensitivity of most low-threshold mechanoreceptor subtypes involved in innocuous touch sensation. Notably, we find that touch and pain sensation are separable, suggesting that as-yet-unknown mechanically activated ion channel(s) must account for noxious (painful) mechanosensation.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Inspired by the self‐migration of microorganisms in nature, artificial micro‐ and nanomotors can mimic this fantastic behavior by converting chemical fuel or external energy into mechanical motion. ...These self‐propelled micro‐ and nanomotors, designed either by top‐down or bottom‐up approaches, are able to achieve different applications, such as environmental remediation, sensing, cargo/sperm transportation, drug delivery, and even precision micro‐/nanosurgery. For these various applications, especially biomedical applications, regulating on‐demand the motion of micro‐ and nanomotors is quite essential. However, it remains a continuing challenge to increase the controllability over motors themselves. Here, we will discuss the recent advancements regarding the motion manipulation of micro‐ and nanomotors by different approaches.
On‐demand regulation of the motion of artificial micro‐ and nanomotors is essential for diverse applications. The recent progress made during the last decade to manipulate the motional behavior of micro‐ and nanomotors by various approaches (such as light, magnetic fields, ultrasound, electric fields, temperature, pH, chemotaxis, and the addition of chemicals) is discussed.
Insufficient resources are associated with negative consequences including decreased valuation of future reinforcers. To determine if these effects result from scarcity, we examined the consequences ...of acute, abrupt changes in resource availability on delay discounting-the subjective devaluation of rewards as delay to receipt increases. In the current study, 599 individuals recruited from Amazon Mechanical Turk read a narrative of a sudden change (positive, neutral, or negative) to one's hypothetical future income and completed a delay discounting task examining future and past monetary gains and losses. The effects of the explicit zero procedure, a framing manipulation, was also examined. Negative income shock significantly increased discounting rates for gains and loses occurring both in the future and the past. Positive income windfalls significantly decreased discounting to a lesser extent. The framing procedure significantly reduced discounting under all conditions. Negative income shocks may result in short-term choices.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Immediately from the outset of the COVID-19 pandemic, researchers from diverse biomedical and biological disciplines have united to study the novel pandemic virus, SARS-CoV-2. The antibody response ...to SARS-CoV-2 has been a major focus of COVID-19 research due to its clinical relevance and importance in vaccine and therapeutic development. Isolation and characterization of antibodies to SARS-CoV-2 have been accumulating at an unprecedented pace. Most of the SARS-CoV-2 neutralizing antibodies to date target the spike (S) protein receptor binding domain (RBD), which engages the host receptor ACE2 for viral entry. Here we review the binding sites and molecular features of monoclonal antibodies that target the SARS-CoV-2 RBD, including a few that also cross-neutralize SARS-CoV.
•The receptor binding domain is a major target of antibodies to SARS-CoV-2.•Neutralizing antibodies target various epitopes on the receptor binding domain.•Convergent antibody responses to SARS-CoV-2 are observed.•Cross-neutralization of SARS-CoV-2 and SARS-CoV maps to two RBD epitopes.•Antibody avidity can be crucial for neutralization potency against SARS-CoV-2.
Rationale
Delay discounting, or the devaluation of delayed outcomes, appears to play an etiological role in tobacco and other substance-use disorders.
Objectives
No human studies to our knowledge ...have been designed to examine whether experimental reductions in delay discounting produce concomitant reduction in drug use.
Methods
Using methods from prior studies on delay discounting and obesity, we examined the effects of episodic future thinking (EFT; a form of mental prospection) on delay discounting and cigarette self-administration in smokers.
Results
Consistent with prior data, EFT significantly reduced both delay discounting (Cohen’s
d
effect size = 0.65) and the number of cigarette puffs earned in a cigarette self-administration task (
d
= 0.58).
Conclusions
The effects of EFT on delay discounting generalize to smokers; EFT also reduces laboratory-based cigarette self-administration. Potential mechanisms of EFT’s effects are discussed as well as implications of EFT for clinical treatment of substance-use disorders.
The hippocampus is essential for encoding self-experienced events into memory. During sleep, neural activity in the hippocampus related to a recent experience has been observed to spontaneously ...reoccur, and this 'replay' has been postulated to be important for memory consolidation. Task-related cues can enhance memory consolidation when presented during a post-training sleep session, and, if memories are consolidated by hippocampal replay, a specific enhancement for this replay should be observed. To test this, we trained rats on an auditory-spatial association task while recording from neuronal ensembles in the hippocampus. We found that, during sleep, a task-related auditory cue biased reactivation events toward replaying the spatial memory associated with that cue. These results indicate that sleep replay can be manipulated by external stimulation and provide further evidence for the role of hippocampal replay in memory consolidation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Learning to Smell Wilson, Donald A; Stevenson, Richard J
2006, 2006-06-06
eBook
Written by a neurobiologist and a psychologist, this volume presents a new theory of olfactory perception. Drawing on research in neuroscience, physiology, and ethology, Donald A. Wilson and Richard ...J. Stevenson address the fundamental question of how we navigate through a world of chemical encounters and provide a compelling alternative to the reception-centric view of olfaction.
The major research challenge in olfaction is determining how the brain discriminates one smell from another. Here, the authors hold that olfaction is generally not a simple physiochemical process, but rather a plastic process that is strongly tied to memory. They find the traditional approach—which involves identifying how particular features of a chemical stimulus are represented in the olfactory system—to be at odds with historical data and with a growing body of neurobiological and psychological evidence that places primary emphasis on synthetic processing and experiential factors.
Wilson and Stevenson propose that experience and cortical plasticity not only are important for traditional associative olfactory memory but also play a critical, defining role in odor perception and that current views are insufficient to account for current and past data.
The book includes a broad comparative overview of the structure and function of olfactory systems, an exploration into the mechanisms of odor detection and olfactory perception, and a discussion of the implications of the authors' theory. Learning to Smell will serve as an important reference for workers within the field of chemical senses and those interested in sensory processing and perception.
Myopia is a common cause of vision loss, with uncorrected myopia the leading cause of distance vision impairment globally. Individual studies show variations in the prevalence of myopia and high ...myopia between regions and ethnic groups, and there continues to be uncertainty regarding increasing prevalence of myopia.
Systematic review and meta-analysis.
We performed a systematic review and meta-analysis of the prevalence of myopia and high myopia and estimated temporal trends from 2000 to 2050 using data published since 1995. The primary data were gathered into 5-year age groups from 0 to ≥100, in urban or rural populations in each country, standardized to definitions of myopia of −0.50 diopter (D) or less and of high myopia of −5.00 D or less, projected to the year 2010, then meta-analyzed within Global Burden of Disease (GBD) regions. Any urban or rural age group that lacked data in a GBD region took data from the most similar region. The prevalence data were combined with urbanization data and population data from United Nations Population Department (UNPD) to estimate the prevalence of myopia and high myopia in each country of the world. These estimates were combined with myopia change estimates over time derived from regression analysis of published evidence to project to each decade from 2000 through 2050.
We included data from 145 studies covering 2.1 million participants. We estimated 1406 million people with myopia (22.9% of the world population; 95% confidence interval CI, 932–1932 million 15.2%–31.5%) and 163 million people with high myopia (2.7% of the world population; 95% CI, 86–387 million 1.4%–6.3%) in 2000. We predict by 2050 there will be 4758 million people with myopia (49.8% of the world population; 3620–6056 million 95% CI, 43.4%–55.7%) and 938 million people with high myopia (9.8% of the world population; 479–2104 million 95% CI, 5.7%–19.4%).
Myopia and high myopia estimates from 2000 to 2050 suggest significant increases in prevalences globally, with implications for planning services, including managing and preventing myopia-related ocular complications and vision loss among almost 1 billion people with high myopia.
Influenza virus evolves rapidly to constantly escape from natural immunity. Most humoral immune responses to influenza virus target the hemagglutinin (HA) glycoprotein, which is the major antigen on ...the surface of the virus. The HA is composed of a globular head domain for receptor binding and a stem domain for membrane fusion. The major antigenic sites of HA are located in the globular head subdomain, which is highly tolerant of amino acid substitutions and continual addition of glycosylation sites. Nonetheless, the evolution of the receptor-binding site and the stem region on HA is severely constrained by their functional roles in engaging the host receptor and in mediating membrane fusion, respectively. Here, we review how broadly neutralizing antibodies (bnAbs) exploit these evolutionary constraints to protect against diverse influenza strains. We also discuss the emerging role of other epitopes that are conserved only in subsets of viruses. This rapidly increasing knowledge of the evolutionary biology, immunology, structural biology, and virology of influenza virus is invaluable for development and design of more universal influenza vaccines and novel therapeutics.
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•Antigenic variation is a major challenge for influenza vaccine design.•Comprehending evolutionary constraints for influenza function is critical for vaccine development.•Broadly neutralizing antibodies reveal conserved epitopes.•Eliciting long-term heterosubtypic immunity is the ultimate goal for vaccine design.
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