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1.
Sci Rep ; 14(1): 8458, 2024 04 30.
Article in English | MEDLINE | ID: mdl-38688951

ABSTRACT

Advances in artificial intelligence (AI) raise important questions about whether people view moral evaluations by AI systems similarly to human-generated moral evaluations. We conducted a modified Moral Turing Test (m-MTT), inspired by Allen et al. (Exp Theor Artif Intell 352:24-28, 2004) proposal, by asking people to distinguish real human moral evaluations from those made by a popular advanced AI language model: GPT-4. A representative sample of 299 U.S. adults first rated the quality of moral evaluations when blinded to their source. Remarkably, they rated the AI's moral reasoning as superior in quality to humans' along almost all dimensions, including virtuousness, intelligence, and trustworthiness, consistent with passing what Allen and colleagues call the comparative MTT. Next, when tasked with identifying the source of each evaluation (human or computer), people performed significantly above chance levels. Although the AI did not pass this test, this was not because of its inferior moral reasoning but, potentially, its perceived superiority, among other possible explanations. The emergence of language models capable of producing moral responses perceived as superior in quality to humans' raises concerns that people may uncritically accept potentially harmful moral guidance from AI. This possibility highlights the need for safeguards around generative language models in matters of morality.


Subject(s)
Artificial Intelligence , Morals , Humans , Artificial Intelligence/ethics , Female , Male , Adult , Young Adult , Middle Aged , Judgment
2.
Addict Behav ; 151: 107949, 2024 04.
Article in English | MEDLINE | ID: mdl-38176326

ABSTRACT

INTRODUCTION: Individuals with serious mental illness (SMI) smoke cigarettes at a much higher rate than the general population, increasing their risk for medical illnesses and mortality. However, individuals with SMI do not get enough support to quit smoking, partially because of concerns from medical providers that reducing smoking may worsen their symptoms or quality of life. METHODS: Veterans with SMI and nicotine dependence (n = 178) completed a 12-week smoking cessation trial (parent trial dates: 2010-2014) including assessments of smoking status, psychiatric symptoms (Brief Psychiatric Rating Scale), and quality of life (Lehman Quality of Life Interview-Short Version) at up to four time points: baseline, post-treatment, three-month follow-up, and 9-month follow-up. Bayesian multilevel modeling estimated the impact of changes in the self-reported number of cigarettes per day in the past seven days on psychiatric symptoms and quality of life. RESULTS: Between subjects, each additional pack of cigarettes smoked per day was associated with a 0.83 point higher score (95%CI: 0.03 to 1.7) on a negative symptoms scale ranging from 0 to 35. Within subjects, each one-pack reduction in the number of cigarettes smoked per day was associated with an improvement of 0.32 (95%CI = 0.12 to 0.54) on the health-related quality of life scale, which ranges from 0 to 7 points. There were no other significant between- or within-subjects effects of smoking on psychiatric symptoms or quality of life. CONCLUSIONS: Individuals with SMI and their providers should pursue smoking cessation without fear of worsening psychiatric symptoms or quality of life.


Subject(s)
Cigarette Smoking , Mental Disorders , Humans , Bayes Theorem , Cigarette Smoking/epidemiology , Cigarette Smoking/therapy , Mental Disorders/psychology , Quality of Life , Smoking/epidemiology , Smoking/therapy
3.
Microorganisms ; 12(1)2024 Jan 04.
Article in English | MEDLINE | ID: mdl-38257929

ABSTRACT

Crayfish plague is a devastating disease of European freshwater crayfish and is caused by the oomycete Aphanomyces astaci (Ap. astaci), believed to have been introduced to Europe around 1860. All European species of freshwater crayfish are susceptible to the disease, including the white-clawed crayfish Austropotamobius pallipes. Ap. astaci is primarily spread by North American crayfish species and can also disperse rapidly through contaminated wet gear moved between water bodies. This spread, coupled with competition from non-indigenous crayfish, has drastically reduced and fragmented native crayfish populations across Europe. Remarkably, the island of Ireland remained free from the crayfish plague pathogen for over 100 years, providing a refuge for A. pallipes. However, this changed in 1987 when a mass mortality event was linked to the pathogen, marking its introduction to the region. Fortunately, crayfish plague was not detected again in Ireland until 2015 when a molecular analysis linked a mass mortality event in the Erne catchment to Ap. astaci. Since then, the pathogen has appeared across the island. Between 2015 and 2023, Ap. astaci was detected in 18 water catchments, revealing multiple genotypes. Intriguingly, the pathogen in Ireland is present without its natural host species. The uneven distribution of various genetic lineages strongly suggests the human-mediated transport of zoospores via contaminated water equipment as a primary cause of spread. This review details the timeline of these events, Ap. astaci's introduction into Ireland, and its rapid spread. As well, this review references the genotypes that have been determined, and discusses the issue of non-indigenous crayfish species in Ireland and management efforts.

4.
Phys Rev E ; 106(4-1): 044201, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36397473

ABSTRACT

We examine a Hamiltonian system which represents an active particle that can move against an opposing external force by drawing energy from an internal depot while immersed in a noisy and dissipative environment. The Hamiltonian consists of two subsystems, one representing the active particle's motion and the other its depot of "fuel." We show that although the active particle loses some of its energy to dissipation from the environment, dissipation can also help to stabilize the dynamical process that makes the particle active. This raises the possibility that the internal mechanisms of active particles may not only be able to operate in noisy and dissipative environments, but may actually rely on the environment for their control.

5.
Hum Relat ; 75(7): 1238-1269, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35634265

ABSTRACT

What motivates managers to deliver bad news in a just manner and why do some managers fail to treat recipients of bad news with dignity and respect? Given the importance of delivering bad news in a just manner, answering these questions is critical to promote justice in the workplace. Drawing on appraisal theories of emotions, we propose that people with higher core self-evaluations may be less likely to deliver bad news in an interpersonally just manner. This is because these actors are more likely to appraise the delivery of bad news as a situation in which they have high coping potential and are therefore less likely to experience anxiety. However, we propose that anxiety can be important for propelling the enactment of interpersonal justice. We test our predictions across three studies (with four samples of full-time managers and employees). Theoretical and practical contributions include enhancing our understanding of who is motivated to enact interpersonal justice, why they are motivated to do so, and how to enhance justice in the workplace. Our findings also challenge the assumption that negative emotions are necessarily dysfunctional for the enactment of interpersonal justice and instead highlight the facilitative role of anxiety in this context.

6.
J Med Libr Assoc ; 110(1): 97-102, 2022 Jan 01.
Article in English | MEDLINE | ID: mdl-35210968

ABSTRACT

OBJECTIVE: This study examines the extent to which retracted articles pertaining to COVID-19 have been shared via social and mass media based on altmetric scores. METHODS: Seventy-one retracted articles related to COVID-19 were identified from relevant databases, of which thirty-nine had an Altmetric Attention Score obtained using the Altmetrics Bookmarklet. Data extracted from the articles include overall attention score and demographics of sharers (e.g., geographic location, professional affiliation). RESULTS: Retracted articles related to COVID-19 were shared tens of thousands of times to an audience of potentially hundreds of millions of readers and followers. Twitter was the largest medium for sharing these articles, and the United States was the country with the most sharers. While general members of the public were the largest proportion of sharers, researchers and professionals were not immune to sharing these articles on social media and on websites, blogs, or news media. CONCLUSIONS: These findings have potential implications for better understanding the spread of misleading or false information perpetuated in retracted scholarly publications. They emphasize the importance of quality peer review and research ethics among journals and responsibility among individuals who wish to share research findings.


Subject(s)
COVID-19 , Social Media , Databases, Factual , Humans , Peer Review , SARS-CoV-2
7.
Front Physiol ; 12: 776826, 2021.
Article in English | MEDLINE | ID: mdl-34867483

ABSTRACT

With approximately 160,000 identified species of butterflies and moths, Lepidoptera are among the most species-rich and diverse insect orders. Lepidopteran insects have fundamental ecosystem functions as pollinators and valuable food sources for countless animals. Furthermore, Lepidoptera have a significant impact on the economy and global food security because many species in their larval stage are harmful pests of staple food crops. Moreover, domesticated species such as the silkworm Bombyx mori produce silk and silk byproducts that are utilized by the luxury textile, biomedical, and cosmetics sectors. Several Lepidoptera have been fundamental as model organisms for basic biological research, from formal genetics to evolutionary studies. Regarding chronobiology, in the 1970s, Truman's seminal transplantation experiments on different lepidopteran species were the first to show that the circadian clock resides in the brain. With the implementation of molecular genetics, subsequent studies identified key differences in core components of the molecular circadian clock of Lepidoptera compared to the dipteran Drosophila melanogaster, the dominant insect species in chronobiological research. More recently, studies on the butterfly Danaus plexippus have been fundamental in characterizing the interplay between the circadian clock and navigation during the seasonal migration of this species. Moreover, the advent of Next Generation Omic technologies has resulted in the production of many publicly available datasets regarding circadian clocks in pest and beneficial Lepidoptera. This review presents an updated overview of the molecular and anatomical organization of the circadian clock in Lepidoptera. We report different behavioral circadian rhythms currently identified, focusing on the importance of the circadian clock in controlling developmental, mating and migration phenotypes. We then describe the ecological importance of circadian clocks detailing the complex interplay between the feeding behavior of these organisms and plants. Finally, we discuss how the characterization of these features could be useful in both pest control, and in optimizing rearing of beneficial Lepidoptera.

8.
Med J (Ft Sam Houst Tex) ; (PB 8-21-04/05/06): 9-13, 2021.
Article in English | MEDLINE | ID: mdl-34251659

ABSTRACT

INTRODUCTION: The US Army's transition from counterinsurgency operations to preparation for large-scale combat operations is likely to bring unique access to care challenges on the battlefield. Ruggedized computer systems exist that allow forward medical personnel to establish telehealth connections with rear-based specialists. We describe our use of one such device during simulated force on force operations at the Joint Readiness Training Center (JRTC). METHODS: Our infantry brigade combat team brought a telehealth device to JRTC 20-02. The device comprised a mobile laptop and peripheral medical devices. We used the Warfighter Information Network-Tactical Increment 2 Tactical Communications Node (TCN) to establish communication between the device and external entities. We sought to establish connectivity in the Fort Polk, LA, cantonment area as part of reception, staging, onward movement, and integration operations. RESULTS: We successfully executed video calls from the field utilizing the telehealth device at the JRTC rear aid station and the local military treatment facility on Fort Polk, LA. We also executed calls to our home station military treatment facility on Fort Carson, CO. Each of these calls lasted approximately five minutes with sustained high-quality video and audio feeds. CONCLUSIONS: Our experience provides proof of concept that telehealth may enable rear-based medical personnel to expand the medical capabilities of medics based forward in the battlespace. Telehealth devices may prove feasible for use with strictly tactical communications architecture in the kinetic setting of large scale combat operations.


Subject(s)
Telemedicine , Communication
9.
Front Hum Neurosci ; 15: 635649, 2021.
Article in English | MEDLINE | ID: mdl-33762916

ABSTRACT

Learning to drive is a significant event for the transition to adulthood and delay or avoidance may have social, practical, and psychological implications. For those with Developmental Coordination Disorder (DCD/Dyspraxia), driving presents a considerable challenge, and the literature shows that there are differences in driving ability between individuals with and without DCD. The aim of the current research is to further our understanding of the mechanisms underlying the driving experiences of individuals with DCD. Nineteen participants with DCD (10 drivers and 9 non-drivers) and 36 controls (17 drivers and 19 non-drivers) aged 18-57 years took part in this study. Participants completed standardized tests, questionnaires and a driving simulation task designed to measure speed, road positioning, and rate of change of steering in three conditions with increasing perceptual complexity. Results indicate that behaviors for all participants changed as the perceptual demands of the task increased. However, drivers with DCD were more affected than all other groups, driving more slowly, and driving further to the right. These findings illustrate how the impact of both internal and external constraints negatively affect the success of the driving task for individuals with DCD compared to their TD peers.

10.
Neuron ; 109(7): 1202-1213.e5, 2021 04 07.
Article in English | MEDLINE | ID: mdl-33609483

ABSTRACT

The frontal cortex, especially the anterior cingulate cortex area (ACA), is essential for exerting cognitive control after errors, but the mechanisms that enable modulation of attention to improve performance after errors are poorly understood. Here we demonstrate that during a mouse visual attention task, ACA neurons projecting to the visual cortex (VIS; ACAVIS neurons) are recruited selectively by recent errors. Optogenetic manipulations of this pathway collectively support the model that rhythmic modulation of ACAVIS neurons in anticipation of visual stimuli is crucial for adjusting performance following errors. 30-Hz optogenetic stimulation of ACAVIS neurons in anesthetized mice recapitulates the increased gamma and reduced theta VIS oscillatory changes that are associated with endogenous post-error performance during behavior and subsequently increased visually evoked spiking, a hallmark feature of visual attention. This frontal sensory neural circuit links error monitoring with implementing adjustments of attention to guide behavioral adaptation, pointing to a circuit-based mechanism for promoting cognitive control.


Subject(s)
Attention/physiology , Frontal Lobe/physiology , Recruitment, Neurophysiological/physiology , Animals , Behavior, Animal , Electroencephalography , Electrophysiological Phenomena , Male , Mice , Mice, Inbred C57BL , Motor Activity/physiology , Neural Pathways/physiology , Neurons/physiology , Optogenetics , Photic Stimulation , Psychomotor Performance/physiology , Reaction Time/physiology , Somatosensory Cortex/physiology , Visual Cortex/physiology
11.
Sci Rep ; 11(1): 2068, 2021 01 22.
Article in English | MEDLINE | ID: mdl-33483591

ABSTRACT

To adapt to their more varied and unpredictable (language) environments, infants from bilingual homes may gather more information (sample more of their environment) by shifting their visual attention more frequently. However, it is not known whether this early adaptation is age-specific or lasts into adulthood. If the latter, we would expect to observe it in adults who acquired their second language early, not late, in life. Here we show that early bilingual adults are faster at disengaging attention to shift attention, and at noticing changes between visual stimuli, than late bilingual adults. In one experiment, participants were presented with the same two visual stimuli; one changed (almost imperceptibly), the other remained the same. Initially, participants looked at both stimuli equally; eventually, they fixated more on the changing stimulus. This shift in looking occurred in the early but not late bilinguals. It suggests that cognitive processes adapt to early bilingual experiences.


Subject(s)
Multilingualism , Adult , Humans , Infant , Language Development , Speech Perception
12.
J Cataract Refract Surg ; 47(1): 111-117, 2021 01 01.
Article in English | MEDLINE | ID: mdl-32815864

ABSTRACT

PURPOSE: To evaluate long-term uveal and capsular biocompatibility of a new fluid-filled modular accommodating intraocular lens (IOL) consisting of base and fluid lenses. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA. DESIGN: Experimental study. METHODS: Bilateral phacoemulsification was performed on 8 rabbits; 1 eye received the test IOL (Juvene) and the other a hydrophobic acrylic control IOL (SA60AT). Slitlamp examinations were performed at postoperative weeks 1 and 4, and at months 2, 3, and 6. The rabbits were killed humanely at 6 months. After gross examination from the Miyake-Apple view, IOLs were removed for implant cytology. All globes were then processed for histopathologic examination. RESULTS: Uveal biocompatibility was similar between test and control IOLs up to 6 months postoperatively. Anterior capsule opacification appeared absent in the test group, and posterior capsule opacification (PCO) was significantly less in comparison with the control group throughout the study. At 6 months, central PCO was scored as 0.12 ± 0.23 with test IOLs and as 4.0 ± 0 with control IOLs (P < .0001, 2-tailed t test: paired 2-sample for means). Histopathologic examination confirmed the relative lack of capsular opacification in test eyes in comparison to controls and the absence of toxicity in any eye. CONCLUSIONS: Six weeks in the rabbit model corresponds to approximately 2 years in the human eye for PCO. In this model, the Juvene IOL maintained an open and expanded capsular bag, preventing overall capsular bag opacification while retaining excellent uveal and capsular biocompatibility.


Subject(s)
Capsule Opacification , Lenses, Intraocular , Multifocal Intraocular Lenses , Phacoemulsification , Acrylic Resins , Animals , Capsule Opacification/prevention & control , Lens Implantation, Intraocular , Postoperative Complications , Prosthesis Design , Rabbits
13.
J Cataract Refract Surg ; 47(2): 238-244, 2021 02 01.
Article in English | MEDLINE | ID: mdl-32818354

ABSTRACT

PURPOSE: To evaluate the ease of replacement and capsular stability of a new fluid-filled, modular, accommodating intraocular lens (IOL) system composed of a monofocal base lens with a fluid lens clipped inside of it. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental study. METHODS: Five New Zealand rabbits underwent bilateral phacoemulsification with implantation of the test lens (Juvene, LensGen, Inc.) in both eyes (4 rabbits), or a control IOL in 1 eye (AcrySof, Alcon Laboratories, Inc.) and the test IOL in the other (1 rabbit). At 2 weeks, the 4 rabbits with bilateral Juvene IOLs had the clipped-in fluid lens exchanged for a new fluid lens in 1 eye, and the base and fluid lenses exchanged for a control lens in the contralateral eye. Slitlamp examinations were performed weekly for 4 weeks. The globes were enucleated and evaluated with ultrasound biomicroscopy, grossly from the posterior Miyake-Apple view, and histopathologically. RESULTS: Explantation/exchange of the fluid lens was considered straightforward by the surgeon. Explantation of the base lens (4) was also safely performed, albeit more demanding, without any signs of damage to the capsular bag under clinical, ultrasound biomicroscopy, and pathological examination in the exchanged eyes. Less capsular bag opacification was observed with the Juvene lens system. CONCLUSIONS: Explantation/exchange of the fluid lens component, or both fluid and base lenses, of this new lens system can be safely accomplished if necessary, because of its modular design and the relative lack of postoperative capsular bag opacification associated with it.


Subject(s)
Capsule Opacification , Lenses, Intraocular , Multifocal Intraocular Lenses , Phacoemulsification , Animals , Lens Implantation, Intraocular , Prosthesis Design , Rabbits
14.
PLoS One ; 15(11): e0232562, 2020.
Article in English | MEDLINE | ID: mdl-33166291

ABSTRACT

Children with Developmental Coordination Disorder (DCD) are diagnosed based on motor difficulties. However, they also exhibit difficulties in several other cognitive domains, including visuospatial processing, executive functioning and attention. One account of the difficulties seen in DCD proposes an impairment in internal forward modelling, i.e., the ability to (i) detect regularities of a repetitive perceptual or motor pattern, (ii) predict future outcomes of motor actions, and (iii) adapt behaviour accordingly. Using electroencephalographic recordings, the present study aimed to delineate these different aspects of internal forward modelling across several domains. To this end, 24 children with DCD and 23 typically-developing children (aged 7-10 years) completed a serial prediction task in the visual, temporal, spatial and motor domains. This task required them to learn short sequences and to indicate whether a sequence was disrupted towards its end. Analyses revealed that, across all domains, children with DCD showed poorer discrimination between intact and disrupted sequences, accompanied by a delayed late parietal positivity elicited by disrupted sequences. These results indicate an impairment in explicit sequence discrimination in DCD across motor and cognitive domains. However, there is no evidence for an impairment in implicit performance on the visuomotor task in DCD. These results suggest an impairment of the updating of an internal forward model in DCD resulting in a blurred representation of that model and, consequently, in a reduced ability to detect regularities in the environment (e.g., sequences). Such a detailed understanding of internal forward modelling in DCD could help to explain the wide range of co-occurring difficulties experienced by those with a diagnosis of DCD.


Subject(s)
Attention/physiology , Executive Function/physiology , Motor Skills Disorders/physiopathology , Movement , Psychomotor Performance , Child , Female , Humans , Learning , Male
15.
R Soc Open Sci ; 7(2): 180191, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32257297

ABSTRACT

Bilinguals purportedly outperform monolinguals in non-verbal tasks of cognitive control (the 'bilingual advantage'). The most common explanation is that managing two languages during language production constantly draws upon, and thus strengthens, domain-general inhibitory mechanisms (Green 1998 Biling. Lang. Cogn. 1, 67-81. (doi:10.1017/S1366728998000133)). However, this theory cannot explain why a bilingual advantage has been found in preverbal infants (Kovacs & Mehler 2009 Proc. Natl Acad. Sci. USA 106, 6556-6560. (doi:10.1073/pnas.0811323106)). An alternative explanation is needed. We propose that exposure to more varied, less predictable (language) environments drive infants to sample more by placing less weight on consolidating familiar information in order to orient sooner to (and explore) new stimuli. To confirm the bilingual advantage in infants and test our proposal, we administered four gaze-contingent eye-tracking tasks to seven- to nine-month-old infants who were being raised in either bilingual (n = 51) or monolingual (n = 51) homes. We could not replicate the finding by Kovacs and Mehler that bilingual but not monolingual infants inhibit learned behaviour (experiment 1). However, we found that infants exposed to bilingual environments do indeed explore more than those exposed to monolingual environments, by potentially disengaging attention faster from one stimulus in order to shift attention to another (experiment 3) and by switching attention more frequently between stimuli (experiment 4). These data suggest that experience-driven adaptations may indeed result in infants exposed to bilingual environments switching attention more frequently than infants exposed to a monolingual environment.

16.
Nat Commun ; 11(1): 1003, 2020 02 21.
Article in English | MEDLINE | ID: mdl-32081848

ABSTRACT

Social isolation during the juvenile critical window is detrimental to proper functioning of the prefrontal cortex (PFC) and establishment of appropriate adult social behaviors. However, the specific circuits that undergo social experience-dependent maturation to regulate social behavior are poorly understood. We identify a specific activation pattern of parvalbumin-positive interneurons (PVIs) in dorsal-medial PFC (dmPFC) prior to an active bout, or a bout initiated by the focal mouse, but not during a passive bout when mice are explored by a stimulus mouse. Optogenetic and chemogenetic manipulation reveals that brief dmPFC-PVI activation triggers an active social approach to promote sociability. Juvenile social isolation decouples dmPFC-PVI activation from subsequent active social approach by freezing the functional maturation process of dmPFC-PVIs during the juvenile-to-adult transition. Chemogenetic activation of dmPFC-PVI activity in the adult animal mitigates juvenile isolation-induced social deficits. Therefore, social experience-dependent maturation of dmPFC-PVI is linked to long-term impacts on social behavior.


Subject(s)
Parvalbumins/physiology , Prefrontal Cortex/physiology , Social Behavior , Animals , Interneurons/physiology , Interpersonal Relations , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Models, Neurological , Models, Psychological , Optogenetics , Parvalbumins/genetics , Prefrontal Cortex/cytology , Prefrontal Cortex/growth & development , Social Isolation
17.
J Med Libr Assoc ; 108(1): 59-66, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31897052

ABSTRACT

OBJECTIVE: This bibliometric study investigated literature pertaining to a quickly growing population worldwide: the oldest-old, individuals age eighty-five and older. The current state of research was surveyed, based on top authors, publishers, authorship networks, themes in publication titles and abstracts, and highly cited publications. METHODS: Bibliographic data was abstracted from the Web of Science database. Microsoft Excel was used for data analyses related to top author, publishers, and terms. VosViewer bibliographic visualization software was used to identify authorship networks. RESULTS: Publications pertaining to the oldest-old have increased dramatically over the past three decades. The majority of these publications are related to medical or genetics topics. Citations for these publications remain relatively low but may be expected to grow in coming years, based on the publication behavior about and increasing prominence of this population. Claudio Franceschi and the Journal of the American Geriatrics Society were found to be the author and journal with the most publications pertaining to the oldest-old, respectively. CONCLUSIONS: The oldest-old is a population of rapidly growing significance. Researchers in library and information science, gerontology, and beyond can benefit themselves and those they serve by participating in research and specialized services to marginalized populations like the oldest-old. This bibliometric study hopefully serves as a launch-point for further inquiry and research in the years to come.


Subject(s)
Abstracting and Indexing/statistics & numerical data , Authorship , Biomedical Research/statistics & numerical data , Frail Elderly/statistics & numerical data , Geriatrics/statistics & numerical data , Publications/statistics & numerical data , Publishing/statistics & numerical data , Aged, 80 and over , Bibliometrics , Female , Humans , Male
18.
Methods Protoc ; 4(1)2020 Dec 29.
Article in English | MEDLINE | ID: mdl-33383791

ABSTRACT

The domestic silkworm Bombyx mori is extensively studied as a model organism for lepidopteran genetics and has an economic value in silk production. Silkworms also have applications in biomedical and cosmetic industries, and the production of mutant B. mori strains significantly enhances basic and applied silkworm research. In recent years, CRISPR/Cas9 technology is being rapidly adopted as the most efficient molecular tool for generating silkworm lines carrying mutations in target genes. Here we illustrate a complete and efficient workflow to screen, characterize rapidly and follow mutations through generations, allowing the generation of B. mori lines, stably inheriting single CRISPR/Cas9-induced mutations. This approach relies on the use of different molecular methods, the heteroduplex assay, cloning followed by Sanger sequencing, and the amplification refractory mutation system PCR. The use of these methodologies in a sequential combination allows the identification of CRISPR/Cas9-induced mutations in genes mapping on both autosomes and sex chromosomes, and the selection of appropriate individuals to found stable mutant B. mori lines. This protocol could be further applied to screen CRISPR/Cas9 mutations in haploid insects.

19.
Int J Mol Sci ; 20(23)2019 Nov 22.
Article in English | MEDLINE | ID: mdl-31766730

ABSTRACT

The alarming escalation of infectious diseases resistant to conventional antibiotics requires urgent global actions, including the development of new therapeutics. Antimicrobial peptides (AMPs) represent potential alternatives in the treatment of multi-drug resistant (MDR) infections. Here, we focus on Cecropins (Cecs), a group of naturally occurring AMPs in insects, and on synthetic Cec-analogs. We describe their action mechanisms and antimicrobial activity against MDR bacteria and other pathogens. We report several data suggesting that Cec and Cec-analog peptides are promising antibacterial therapeutic candidates, including their low toxicity against mammalian cells, and anti-inflammatory activity. We highlight limitations linked to the use of peptides as therapeutics and discuss methods overcoming these constraints, particularly regarding the introduction of nanotechnologies. New formulations based on natural Cecs would allow the development of drugs active against Gram-negative bacteria, and those based on Cec-analogs would give rise to therapeutics effective against both Gram-positive and Gram-negative pathogens. Cecs and Cec-analogs might be also employed to coat biomaterials for medical devices as an approach to prevent biomaterial-associated infections. The cost of large-scale production is discussed in comparison with the economic and social burden resulting from the progressive diffusion of MDR infectious diseases.


Subject(s)
Antimicrobial Cationic Peptides , Drug Resistance, Multiple, Bacterial , Gram-Negative Bacteria/immunology , Gram-Negative Bacterial Infections , Insect Proteins , Antimicrobial Cationic Peptides/immunology , Antimicrobial Cationic Peptides/therapeutic use , Drug Resistance, Multiple, Bacterial/drug effects , Drug Resistance, Multiple, Bacterial/immunology , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/immunology , Humans , Insect Proteins/therapeutic use
20.
ACS Infect Dis ; 5(7): 1200-1213, 2019 07 12.
Article in English | MEDLINE | ID: mdl-31045339

ABSTRACT

Pseudomonas aeruginosa is an opportunistic bacterial pathogen causing severe infections in hospitalized and immunosuppressed patients, particularly individuals affected by cystic fibrosis. Several clinically isolated P. aeruginosa strains were found to be resistant to three or more antimicrobial classes indicating the importance of identifying new antimicrobials active against this pathogen. Here, we characterized the antimicrobial activity and the action mechanisms against P. aeruginosa of two natural isoforms of the antimicrobial peptide cecropin B, both isolated from the silkworm Bombyx mori. These cecropin B isoforms differ in a single amino acid substitution within the active portion of the peptide, so that the glutamic acid of the E53 CecB variant is replaced by a glutamine in the Q53 CecB isoform. Both peptides showed a high antimicrobial and membranolytic activity against P. aeruginosa, with Q53 CecB displaying greater activity compared with the E53 CecB isoform. Biophysical analyses, live-cell NMR, and molecular-dynamic-simulation studies indicated that both peptides might act as membrane-interacting elements, which can disrupt outer-membrane organization, facilitating their translocation toward the inner membrane of the bacterial cell. Our data also suggest that the amino acid variation of the Q53 CecB isoform represents a critical factor in stabilizing the hydrophobic segment that interacts with the bacterial membrane, determining the highest antimicrobial activity of the whole peptide. Its high stability to pH and temperature variations, tolerance to high salt concentrations, and low toxicity against human cells make Q53 CecB a promising candidate in the development of CecB-derived compounds against P. aeruginosa.


Subject(s)
Amino Acid Substitution , Anti-Infective Agents/pharmacology , Bombyx/metabolism , Insect Proteins/pharmacology , Pseudomonas aeruginosa/drug effects , Animals , Bacterial Outer Membrane/drug effects , Bombyx/genetics , Drug Resistance, Multiple, Bacterial/drug effects , Drug Stability , Hydrophobic and Hydrophilic Interactions , Insect Proteins/genetics , Microbial Sensitivity Tests , Models, Molecular , Molecular Dynamics Simulation , Protein Isoforms/genetics , Protein Isoforms/pharmacology , Thermodynamics
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