Eukaryotic cells have a layer of heterochromatin at the nuclear periphery. To investigate mechanisms regulating chromatin distribution, we analyzed heterochromatin organization in different tissues ...and species, including mice with mutations in the lamin B receptor (Lbr) and lamin A (Lmna) genes that encode nuclear envelope (NE) proteins. We identified LBR- and lamin-A/C-dependent mechanisms tethering heterochromatin to the NE. The two tethers are sequentially used during cellular differentiation and development: first the LBR- and then the lamin-A/C-dependent tether. The absence of both LBR and lamin A/C leads to loss of peripheral heterochromatin and an inverted architecture with heterochromatin localizing to the nuclear interior. Myoblast transcriptome analyses indicated that selective disruption of the LBR- or lamin-A-dependent heterochromatin tethers have opposite effects on muscle gene expression, either increasing or decreasing, respectively. These results show how changes in NE composition contribute to regulating heterochromatin positioning, gene expression, and cellular differentiation during development.
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► LBR- and lamin-A/C-dependent tethers maintain peripheral heterochromatin ► In their absence, all heterochromatin clusters in the nuclear interior ► During cellular differentiation, the LBR tether precedes the lamin A/C tether ► Lamin A/C promotes, whereas LBR delays myogenic differentiation
The lamin B receptor and lamin A/C have sequential roles in the tethering of peripheral heterochromatin during cellular differentiation, corresponding to their differential effects on heterochromatin positioning and transcription of tissue-specific genes.
The nuclear lamina is an important structural determinant for the nuclear envelope as a whole, attaching chromatin domains to the nuclear periphery and localizing some nuclear envelope proteins. The ...major components of the lamina are the A-type and B-type lamins, which are members of the intermediate filament protein family. Whereas the expression of A-type lamins is developmentally regulated, B-type lamins, as a class, are found in all cells. The association of B-type lamins with many aspects of nuclear function has led to the view that these are essential proteins, and there is growing evidence suggesting that they regulate cellular senescence. However, B-type lamins are dispensable in certain cell types in vivo, and neither A-type nor B-type lamins may be required in early embryos or embryonic stem cells. The picture that is beginning to emerge is of a complex network of interactions at the nuclear periphery that may be defined by cell- and tissue-specific functions.
Purpose
This paper aims to examine how consumers respond to social media influencers that are created through artificial intelligence (AI) and compares effects to traditional (human) influencers.
...Design/methodology/approach
Across two empirical studies, the authors examine the efficacy of AI social media influencers. With Study 1, the authors establish baseline effects for AI influencers and investigate how social-psychological distance impacts consumer perceptions. The authors also investigate the role of an influencer’s agency – being autonomous or externally managed – to test the boundaries of the results and determine the interactive effects between influencer type and influencer agency. Study 2 acts as an extension and validation of Study 1, whereby the authors provide generalisability and overlay the role of need for uniqueness as a moderated mediator.
Findings
The authors show that there are similarities and differences in the ways in which consumers view AI and human influencers. Importantly, the authors find no difference in terms of intention to follow or personalisation. This suggests that consumers are equally open to follow an AI or human influencer, and they perceive the level of personalisation provided by either influencer type as similar. Furthermore, while an AI influencer is generally perceived as having lower source trust, they are more likely to evoke word-of-mouth intentions. In understanding these effects, the authors show that social distance mediates the relationship between influencer type and the outcomes the authors investigate. Results also show that AI influencers can have a greater effect on consumers who have a high need for uniqueness. Finally, the authors find that a lack of influencer agency has a detrimental effect.
Research limitations/implications
The studies investigate consumers’ general response to AI influencers within the context of Instagram, however, future research might examine consumers’ response to posts promoting specific products across a variety of category contexts and within different social media platforms.
Practical implications
The authors find that in some ways, an AI influencer can be as effective as a human influencer. Indeed, the authors suggest that there may be a spill-over effect from consumer experiences with other AI recommendation systems, meaning that consumers are open to AI influencer recommendations. However, the authors find consistent evidence that AI influencers are trusted less than traditional influencers, hence the authors caution brands from rushing to replace human influencers with their AI counterparts.
Originality/value
This paper offers novel insight into the increasingly prominent phenomenon of the AI influencer. Specifically, it takes initial steps towards developing understanding as to how consumers respond to AI influencers and contrast these effects with human influencers.
Biomarker discovery and development for clinical research, diagnostics and therapy monitoring in clinical trials have advanced rapidly in key areas of medicine - most notably, oncology and ...cardiovascular diseases - allowing rapid early detection and supporting the evolution of biomarker-guided, precision-medicine-based targeted therapies. In Alzheimer disease (AD), breakthroughs in biomarker identification and validation include cerebrospinal fluid and PET markers of amyloid-β and tau proteins, which are highly accurate in detecting the presence of AD-associated pathophysiological and neuropathological changes. However, the high cost, insufficient accessibility and/or invasiveness of these assays limit their use as viable first-line tools for detecting patterns of pathophysiology. Therefore, a multistage, tiered approach is needed, prioritizing development of an initial screen to exclude from these tests the high numbers of people with cognitive deficits who do not demonstrate evidence of underlying AD pathophysiology. This Review summarizes the efforts of an international working group that aimed to survey the current landscape of blood-based AD biomarkers and outlines operational steps for an effective academic-industry co-development pathway from identification and assay development to validation for clinical use.
A major unanswered question in the dementia field is whether cognitively unimpaired individuals who harbor both Alzheimer's disease neuropathological hallmarks (that is, amyloid-β plaques and tau ...neurofibrillary tangles) can preserve their cognition over time or are destined to decline. In this large multicenter amyloid and tau positron emission tomography (PET) study (n = 1,325), we examined the risk for future progression to mild cognitive impairment and the rate of cognitive decline over time among cognitively unimpaired individuals who were amyloid PET-positive (A
) and tau PET-positive (T
) in the medial temporal lobe (A
T
) and/or in the temporal neocortex (A
T
) and compared them with A
T
and A
T
groups. Cox proportional-hazards models showed a substantially increased risk for progression to mild cognitive impairment in the A
T
(hazard ratio (HR) = 19.2, 95% confidence interval (CI) = 10.9-33.7), A
T
(HR = 14.6, 95% CI = 8.1-26.4) and A
T
(HR = 2.4, 95% CI = 1.4-4.3) groups versus the A
T
(reference) group. Both A
T
(HR = 6.0, 95% CI = 3.4-10.6) and A
T
(HR = 7.9, 95% CI = 4.7-13.5) groups also showed faster clinical progression to mild cognitive impairment than the A
T
group. Linear mixed-effect models indicated that the A
T
(β = -0.056 ± 0.005, T = -11.55, P < 0.001), A
T
(β = -0.024 ± 0.005, T = -4.72, P < 0.001) and A
T
(β = -0.008 ± 0.002, T = -3.46, P < 0.001) groups showed significantly faster longitudinal global cognitive decline compared to the A
T
(reference) group (all P < 0.001). Both A
T
(P < 0.001) and A
T
(P = 0.002) groups also progressed faster than the A
T
group. In summary, evidence of advanced Alzheimer's disease pathological changes provided by a combination of abnormal amyloid and tau PET examinations is strongly associated with short-term (that is, 3-5 years) cognitive decline in cognitively unimpaired individuals and is therefore of high clinical relevance.
Agriculture is expanding into regions that are affected by salinity. This review considers the energetic costs of salinity tolerance in crop plants and provides a framework for a quantitative ...assessment of costs. Different sources of energy, and modifications of root system architecture that would maximize water vs ion up take are addressed. Energy requirements for transport of salt (NaCl) to leaf vacuoles for osmotic adjustment could be small if there are no substantial leaks back across plasma membrane and tonoplast in root and leaf. The coupling ratio of the H⁺ -ATPase also is a critical component. One proposed leak, that of Na⁺ influx across the plasma membrane through certain aquaporin channels, might be coupled to water flow, thus conserving energy. For the tonoplast, control of two types of cation channels is required for energy efficiency. Transporters controlling the Na⁺ and Cl⁻ concentrations in mitochondria and chloroplasts are largely unknown and could be a major energy cost. The complexity of the system will require a sophisticated modelling approach to identify critical transporters, apoplastic barriers and root structures. This modelling approach will inform experimentation and allow a quantitative assess ment of the energy costs of Na Cl tolerance to guide breeding and engineering of molecular components.
Historically, sea ice concentration (SIC) has been measured through the use of passive microwave sensors, as well as human interpretation of synthetic aperture radar (SAR). Although passive microwave ...data are processed automatically, it suffers from poor spatial resolution and the higher frequency channels are sensitive to weather conditions. Deep learning has demonstrated its ability to perform complex and accurate analysis of images; here, we apply deep learning to estimate ice concentration from SAR scenes. We developed a deep convolutional neural network (CNN) that predicts SIC from SAR, trained upon passive microwave data. The model achieves a 5.24%/7.87% error on its train and test set, respectively. To assess the real-world applicability, we performed an independent validation on 18 SAR scenes (from two distinct geographical regions), not previously seen during training or test. Comparing against human-generated ice analysis charts, we achieved an <inline-formula> <tex-math notation="LaTeX">L1 </tex-math></inline-formula> error of 0.2059, competitive with passive microwave (<inline-formula> <tex-math notation="LaTeX">E_{L1} = 0.1863 </tex-math></inline-formula>) for the Canadian Arctic Archipelago. For the Gulf of Saint Lawrence region, we achieved an <inline-formula> <tex-math notation="LaTeX">L1 </tex-math></inline-formula> error of 0.2653, significantly better than the passive microwave result (<inline-formula> <tex-math notation="LaTeX">E_{L1} = 0.3593 </tex-math></inline-formula>). By using novel techniques for model training, as well as training entirely upon passive microwave data, we present an accessible and robust method of developing similar systems for processing SAR.<xref ref-type="fn" rid="fn1"> 1 Our results suggest that with further postprocessing, CNNs are accurate and robust enough to be used for operational tasks. 1
Code available: https://github.com/clvcooke/Estimating-SIC-from-SAR-github.com/clvcooke/Estimating-SIC-from-SAR
Abstract
Background
The need to call out and expose authors for their persistence in improperly using epidemiology has been previously noted. Tsuda et al. have done well to expose Schüz et al.’s ...arguments/assertions in their recent publication in
Environmental Heath
. In this Comment, I point out that, also warranting being called out, are the arguments/assertions of Cléro et al. who, in their recent response to an article by Tsuda et al., reiterated the conclusions and recommendations derived from their European project, which were published in
Environment International
in 2021.
Tsuda et al. had critiqued the Cléro et al. 2021 publication in their 2022 review article. However, in their response to it, Cléro et al. deflected by not addressing any of the key points that Tsuda et al. had made in their review regarding the aftermath of the Chernobyl and Fukushima nuclear accidents. In this Comment, I critique Cléro et al.’s inadequate response.
Publication of this Comment will help in routing out the improper use of epidemiology in the formulation of public health policy and thereby reduce the influence of misinformation on both science and public policy. My critique of Cléro et al. is not dissimilar from Tsuda et al.’s critique of Schüz et al.: in as much as Schüz et al. should withdraw their work, so should Cléro et al.’s article be retracted.
Main body
The response by Cléro et al. consists of four paragraphs. First was their assertion that the purpose of the SHAMISEN project was to make recommendations based on scientific evidence and that it was not a systematic review of all related articles. I point out that the Cléro et al. recommendations were not based on objective scientific evidence, but on biased studies.
In the second paragraph, Cléro et al. reaffirmed the SHAMISEN Consortium report, which claimed that the overdiagnosis observed in non-exposed adults was applicable to children because children are mirrors of adults. However, the authors of that report withheld statements about secondary examinations in Fukushima that provided evidence against overdiagnosis.
In the third paragraph, Cléro et al. provided an explanation regarding their disclosure of conflicting interests, which was contrary to professional norms for transparency and thus was unacceptable.
Finally, their insistence that the Tsuda et al. study was an ecological study susceptible to “the ecological fallacy” indicated their lack of epidemiological knowledge about ecological studies. Ironically, many of the papers cited by Cléro et al. regarding overdiagnosis were, in fact, ecological studies.
Conclusion
Cléro et al. and the SHAMISEN Consortium should withdraw their recommendation “not to launch a mass thyroid cancer screening after a nuclear accident, but rather to make it available (with appropriate information counselling) to those who request it.” Their recommendation is based on biased evidence and would cause confusion regarding public health measures following a nuclear accident. Those authors should, in my assessment, acquaint themselves with modern epidemiology and evidence-based public health. Like Tsuda et al. recommended of Schüz et al., Cléro et al. ought also to retract their article.
In The Lancet Neurology, Yakeel Quiroz and colleagues1 convincingly show the correlations between plasma neurofilament light chain (NfL) concentrations and age and genetic status in a very large ...cohort of 1070 presenilin 1 (PSEN1) E280A (Glu280Ala) mutation carriers and 1074 age-matched non-carriers from the autosomal dominant Alzheimer's disease kindred in Antioquia, Colombia. The advent of new technologies (eg, mass spectroscopy and single molecule assays on magnetic beads) and better performing antibodies for immunoassays are transforming the ability to detect Alzheimer's disease at its preclinical, prodromal, and clinical stages.4–7 These new assays for amyloid β1–42 and phosphorylated tau 181 are now operating at low picomolar concentrations, and show increased sensitivity and specificity over earlier assays. The clinical prediction of age at symptoms onset and rate of progression for sporadic Alzheimer's disease or autosomal dominant Alzheimer's disease will soon be feasible in individuals at the preclinical stage.
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