Miracle-dz/UniFAR-FTUs huggingface dataset:
Analyzing efficacy, stability, and safety of AAV-mediated optogenetic hearing restoration in mice

This longitudinal study revealed stable expression of the fast-gating channelrhodopsin f-Chrimson in cochlear neurons of mice over at least 2 yr upon a single postnatal AAV dosing of the cochlea. AAV-mediated optogenetic neural stimulation has become a clinical approach for restoring function in sensory disorders and feasibility for hearing restoration has been indicated in rodents. Nonetheless, long-term stability and safety of AAV-mediated channelrhodopsin (ChR) expression in spiral ganglion neurons (SGNs) remained to be addressed. Here, we used longitudinal studies on mice subjected to early postnatal administration of AAV2/6 carrying fast gating ChR f-Chrimson under the control of the human synapsin promoter unilaterally to the cochlea. f-Chrimson expression in SGNs in both ears and the brain was probed in animals aged 1 mo to 2 yr. f-Chrimson was observed in SGNs at all ages indicating longevity of ChR-expression. SGN numbers in the AAV-injected cochleae declined with age faster than in controls. Investigations were extended to the brain in which viral transduction was observed across the organ at varying degrees irrespective of age without observing viral spread-related pathologies. No viral DNA or virus-related histopathological findings in visceral organs were encountered. In summary, our study demonstrates life-long (24 mo in mice) expression of f-Chrimson in SGNs upon single AAV-dosing of the cochlea. Graphical Abstract
A Comparison of Pollen and Syrup Exposure Routes in Bombus impatiens (Hymenoptera: Apidae) Microcolonies: Implications for Pesticide Risk Assessment

Abstract Bumble bees are important pollinators for both native plants and managed agricultural systems. Accumulating evidence has shown that pesticides, including neonicotinoids, can have a range of adverse effects on bumble bee health. Most laboratory studies that assess the effects of chronic neonicotinoid exposure on bumble bees use syrup as the delivery vehicle, rather than pollen. However, in the field, it is likely that bumble bees are exposed to neonicotinoids in both nectar (syrup) and pollen. To examine the potential for different effects based on the vehicle, we compared two studies of chronic exposure to the neonicotinoid acetamiprid in Bombus impatiens microcolonies. We examined correlations between microcolony endpoints and identified associations between the timing of colony pollen and syrup consumption and drone production. Furthermore, in line with previous results, we found that average drone weight was affected at a range of doses only when microcolonies were exposed to acetamiprid via pollen. In general, our analyses point to the importance of the treatment vehicle and suggest that critical effects on developing brood could be missed when neonicotinoid exposure occurs only through syrup.
Tunable and state-preserving frequency conversion of single photons in hydrogen

In modern quantum technologies, preservation of the photon statistics of quantum optical states upon frequency conversion holds the key to the viable implementation of quantum networks, which often require interfacing of several subsystems operating in widely different spectral regions. Most current approaches offer only very small frequency shifts and limited tunability, while suffering from high insertion loss and Raman noise originating in the materials used. We introduce a route to quantum-correlation–preserving frequency conversion using hydrogen-filled antiresonant-reflecting photonic crystal fibers. Transient optical phonons generated by stimulated Raman scattering enable selective frequency up-conversion by 125 terahertz of the idler photon of an entangled pair, with efficiencies up to 70%. This threshold-less molecular modulation process preserves quantum correlations, making it ideal for applications in quantum information. Description A quantum frequency converter Practical quantum technologies require interfacing of several subsystems operating in widely different spectral regions. However, most current approaches offer only very small frequency shifts and limited tunability. Tyumenev et al. demonstrate efficient (up to 70%) quantum state–preserving photon frequency up-conversion by molecular modulation in hydrogen gas–filled antiresonant photonic crystal fibers (see the Perspective by Sokolov). By combining a high-intensity coherent pump pulse with a (low-intensity) quantum source based on parametric down-conversion (generating pairs of signal and idler photons), the authors show that the idler photons can be up-converted by 125 terahertz using a Raman-scattering process. The process is general and should be applicable to other quantum sources. —ISO Hollow-core photonic crystal fibers filled with hydrogen can efficiently upconvert single photons by 125 terahertz.
FTO mediates LINE1 m6A demethylation and chromatin regulation in mESCs and mouse development

N6-methyladenosine (m6A) is the most abundant internal modification on mammalian messenger RNA. It is installed by a writer complex and can be reversed by erasers such as the fat mass and obesity-associated protein FTO. Despite extensive research, the primary physiological substrates of FTO in mammalian tissues and development remain elusive. Here, we show that FTO mediates m6A demethylation of long-interspersed element-1 (LINE1) RNA in mouse embryonic stem cells (mESCs), regulating LINE1 RNA abundance and the local chromatin state, which in turn modulates the transcription of LINE1-containing genes. FTO-mediated LINE1 RNA m6A demethylation also plays regulatory roles in shaping chromatin state and gene expression during mouse oocyte and embryonic development. Our results suggest broad effects of LINE1 RNA m6A demethylation by FTO in mammals. Description Demethylation controls development FTO was the first discovered RNA demethylase that reverses messenger RNA N6-methyladenosine (m6A) modification. Despite numerous past studies, the physiological substrates of FTO in mammalian development remain unclear. Wei et al. uncovered RNA transcribed from long-interspersed element-1 (LINE1), one of the most abundant mammalian retrotransposons, as a major substrate of FTO in mouse embryonic stem cells and mouse tissues. m6A demethylation by FTO regulates LINE1 RNA level, which shapes local and global chromatin state. Deletion of Fto in cells deactivates LINE1-containing genes by repressing intragenic LINE1 RNA. This FTO-LINE1 RNA axis also affects mouse oocyte and embryonic development. —BAP The FTO protein mediates demethylation of long-interspersed element-1 RNA in embryonic stem cells.
The chaperone Clusterin in neurodegeneration−friend or foe?

Fibrillar protein aggregates are the pathological hallmark of a group of age‐dependent neurodegenerative conditions, including Alzheimer's and Parkinson's disease. Aggregates of the microtubule‐associated protein Tau are observed in Alzheimer's disease and primary tauopathies. Tau pathology propagates from cell to cell in a prion‐like process that is likely subject to modulation by extracellular chaperones such as Clusterin. We recently reported that Clusterin delayed Tau fibril formation but enhanced the activity of Tau oligomers to seed aggregation of endogenous Tau in a cellular model. In contrast, Clusterin inhibited the propagation of α‐Synuclein aggregates associated with Parkinson's disease. These findings raise the possibility of a mechanistic link between Clusterin upregulation observed in Alzheimer's disease and the progression of Tau pathology. Here we review the diverse functions of Clusterin in the pathogenesis of neurodegenerative diseases, focusing on evidence that Clusterin may act either as a suppressor or enhancer of pathology.
CRISPR-Cas9 editing of the arginine–vasopressin V1a receptor produces paradoxical changes in social behavior in Syrian hamsters

Significance Arginine–vasopressin (AVP) acting on V1a receptors (Avpr1as) represents a key signaling mechanism in a brain circuit that increases the expression of social communication and aggression. We produced Syrian hamsters that completely lack Avpr1as (Avpr1a knockout [KO] hamsters) using the CRISPR-Cas9 system to more fully examine the role of Avpr1a in the expression of social behaviors. We confirmed the absence of Avpr1as in these hamsters by demonstrating 1) a complete lack of Avpr1a-specific receptor binding throughout the brain, 2) a behavioral insensitivity to centrally administered AVP, and 3) an absence of the well-known blood-pressure response produced by activating Avpr1as. Unexpectedly, however, Avpr1a KO hamsters displayed more social communication behavior and aggression toward same-sex conspecifics than did their wild-type (WT) littermates.
Parasite defensive limb movements enhance acoustic signal attraction in male little torrent frogs

Many animals rely on complex signals that target multiple senses to attract mates and repel rivals. These multimodal displays can however also attract unintended receivers, which can be an important driver of signal complexity. Despite being taxonomically widespread, we often lack insight into how multimodal signals evolve from unimodal signals and in particular what roles unintended eavesdroppers play. Here, we assess whether the physical movements of parasite defense behavior increase the complexity and attractiveness of an acoustic sexual signal in the little torrent frog (Amolops torrentis). Calling males of this species often display limb movements in order to defend against blood-sucking parasites such as frog-biting midges that eavesdrop on their acoustic signal. Through mate choice tests we show that some of these midge-evoked movements influence female preference for acoustic signals. Our data suggest that midge-induced movements may be incorporated into a sexual display, targeting both hearing and vision in the intended receiver. Females may play an important role in incorporating these multiple components because they prefer signals which combine multiple modalities. Our results thus help to understand the relationship between natural and sexual selection pressure operating on signalers and how in turn this may influence multimodal signal evolution.
Change of Direction Speed in Youth Male Soccer Players: The Predictive Value of Anthropometrics and Biological Maturity.

This study aimed to develop the optimal allometric body size/shape and a biological maturity model that predicted the change of direction (CoD) mean speed performance in youth male soccer players. One-hundred and fifteen youth soccer players (age: 12.4 [1.3] y) participated in this study. The 505 test was used to assess CoD mean speed performance. Anthropometric measurements comprised body height (cm), sitting height (cm), body mass (kg), fat mass (kg), lower limb length (cm), thigh length (cm), leg length (cm), foot length (cm), thigh girth (cm), and calf girth (cm). The maturity status was determined based on the maturity offset method. To identify size/shape and maturity characteristics associated with CoD speed performance, we computed a multiplicative allometric log-linear regression model, which was refined using backward elimination. The multiplicative allometric model exploring the association between 505 CoD mean speed performance and the different anthropometric characteristics in youth soccer players estimated that fat mass (P < .001), sitting height (P = .02), and maturity offset (P = .004) are the key predictors. More specifically, youths who are more mature and have a lower fat mass and a shorter trunk length, are likely to achieve a better CoD mean speed performance. These findings highlight the relevance of considering anthropometric and maturity characteristics in youth soccer players to support talent identification.
Exertional heat stroke: nutritional considerations

What is the topic of this review? The potential role of nutrition in exertional heat stroke. What advances does it highlight? Certain nutritional and dietary strategies used by athletes and workers may exert a protective effect the pathophysiological processes of exertional heat stroke, whereas others may be detrimental. While current evidence suggests that some of these practices may be leveraged as a potential countermeasure to exertional heat stroke, further research on injury‐related outcomes in humans is required.
Wnt11 acts on dermomyotome cells to guide epaxial myotome morphogenesis

The dorsal axial muscles, or epaxial muscles, are a fundamental structure covering the spinal cord and vertebrae, as well as mobilizing the vertebrate trunk. To date, mechanisms underlying the morphogenetic process shaping the epaxial myotome are largely unknown. To address this, we used the medaka zic1/zic4-enhancer mutant Double anal fin (Da), which exhibits ventralized dorsal trunk structures resulting in impaired epaxial myotome morphology and incomplete coverage over the neural tube. In wild type, dorsal dermomyotome (DM) cells reduce their proliferative activity after somitogenesis. Subsequently, a subset of DM cells, which does not differentiate into the myotome population, begins to form unique large protrusions extending dorsally to guide the epaxial myotome dorsally. In Da, by contrast, DM cells maintain the high proliferative activity and mainly form small protrusions. By combining RNA- and ChIP-sequencing analyses, we revealed direct targets of Zic1, which are specifically expressed in dorsal somites and involved in various aspects of development, such as cell migration, extracellular matrix organization, and cell-cell communication. Among these, we identified wnt11 as a crucial factor regulating both cell proliferation and protrusive activity of DM cells. We propose that dorsal extension of the epaxial myotome is guided by a non-myogenic subpopulation of DM cells and that wnt11 empowers the DM cells to drive the coverage of the neural tube by the epaxial myotome.
Resolvin D1 Inhibits Corneal Inflammation in Staphylococcus Aureus Keratitis

ABSTRACT Purpose To investigate the role of lipid mediator, resolvin D1 (RvD1), in corneal inflammation. Methods The anti-inflammatory effect of RvD1 on stimulated human corneal epithelial cells (HCECs) was assessed. C57BL/6 mice corneas were abraded and treated with RvD1 after stimulation with Staphylococcus aureus. Cytokine levels in the corneas, cervical drainage lymph nodes (DLNs), and spleens were measured. Anterior segment photography and optical coherence tomography quantified the changes in corneal thickness and haziness. Neutrophil infiltration in the cornea was examined by haematoxylin and eosin (H&E) staining and immunohistochemistry. Results RvD1 significantly inhibited cytokine production in HCECs and mouse corneas, cervical DLNs, and spleens while stimulating interleukin-10 (IL-10) production. Corneal opacity development, thickening, and neutrophil infiltration significantly reduced in response to RvD1 stimulation in the S. aureus-infected mice corneas. Conclusion RvD1 inhibited S. aureus-induced corneal inflammation. These results potentiate RvD1 as an anti-inflammatory therapy for patients with corneal inflammation induced by bacterial keratitis.
Temporal variation of high‐level pyrethroid resistance in the major malaria vector Anopheles gambiae s.l. in Yaoundé, Cameroon, is mediated by target‐site and metabolic resistance

Constant assessment of insecticide resistance levels is mandatory to implement adequate malaria control tools, but little information is available on the annual dynamics of resistance. We, therefore, monitored variations in resistance in Anopheles gambiae s.l. over four seasons during 2 years in two localities of Yaoundé: urban Etoa‐Meki and peri‐urban Nkolondom. Mosquitoes were collected seasonally at larval stage and reared to adults for insecticide susceptibility tests and molecular analysis of resistance mechanisms. Anopheles coluzzii was found in Etoa‐Meki and An. gambiae in Nkolondom. Low mortalities to pyrethroids were observed (permethrin <10%, deltamethrin <21%), and resistance extended to 5× and 10× diagnostic doses, revealing a marked increase compared to previous studies. A seasonal variation in resistance was observed with the highest levels within dry seasons in Etoa‐Meki and rainy seasons in Nkolondom. The 1014F kdr allele shows a high frequency (0.9), associated with overexpression of metabolic genes (Cyp6M2, Cyp6P4, Cyp9K1, Cyp6Z1, and Cyp6Z2) varying significantly seasonally. This study reveals an escalation in resistance to pyrethroids in Yaoundé's malaria vectors with seasonal variations. An adequate choice of the implementation period of punctual vector control actions according to the resistance profile will help to potentiate the desired effect and thus improve its efficiency.
Geek Heresy: Rescuing Social Change from the Cult of Technology

Kentaro Toyama was a self-described â€œtechnoholicâ€ and award-winning computer scientist whose research paved the way for cutting-edge products like Microsoftâ€™s Kinect. In 2004, he co-founded Microsoft Research India, and he set his mind to design electronic inventions to improve education, agriculture, health care, and governance in the developing worldâ€™s poorest communities. What Toyama experienced in India, though, shook his faith in technology. Â At a school outside Bangalore, Toyama saw computers locked away in a dusty cabinet because teachers didnâ€™t know what to do with them. Mobile-phone projects to disseminate health information routinely failed. â€œTelecentersâ€ intended to teach rural farmers better agriculture devolved into places for sleazy web surfing. Meanwhile back in the United States, Silicon Valley executives who evangelize novel technologies at work sent their children to Waldorf schools that ban electronics. And, four decades of incredible innovation have done nothing to turn the tide of increasing poverty and inequality. Why then, do we keep hoping that technology will solve our greatest social challenges? In this talk, Toyama inoculates us against the rhetoric of digital utopians and reinvigorates us with a genuinely human paradigm for social change. A heretic among technologists, Toyama is uniquely able to reveal why social progress depends on human changes that gadgets just canâ€™t deliver. He provides a fierce critique and a heartwarming reminder that itâ€™s human wisdom, not machines, that move our world forward. Â
The Life Course of Unemployment and Midlife Health

Objectives: We estimate associations between unemployment trajectories from ages 27-49 and physical and mental health at age 50. Methods: Data are from the U.S. National Longitudinal Survey of Youth, 1979 (N=6434). Group-based trajectory models are used to identify unemployment trajectories. Generalized linear models with a modified Bolck, Croon, and Hagenaars (BCH) correction are used to regress health on unemployment trajectory groups. Results: We identified “Consistently Low (70%),” “Decreasing Mid-Career (18%),” and “Persistently High (12%)” unemployment trajectories. Experiencing Decreasing Mid-Career or Persistently High trajectories was associated with worse physical and mental health at age 50 than Consistently Low trajectories. Experiencing a Persistently High trajectory was associated with worse physical and mental health than a Decreasing Mid-Career trajectory. Discussion: Timing and likelihood of unemployment are associated with midlife health. Mid-Career unemployment is associated with worse physical and mental health at age 50, but not to the same degree as Persistently High unemployment.
Sex difference in disease burden of inflammatory arthritis patients treated with tumor necrosis factor inhibitors as part of standard care

Objective Knowledge is needed on the total disease burden across the sexes in inflammatory arthritis (IA). We aimed to compare disease burden, including a broad range of health aspects, across men and women with IA treated with tumor necrosis factor inhibitors (TNFi). Methods Adult outpatients with IA (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis) were included as part of standard care. Patient-reported outcomes, disease activity, TNFi trough levels, calprotectin, Work Productivity and Activity Impairment, comorbidities and cardiovascular risk profile were assessed. Unadjusted comparisons across sexes were done with independent t-test, Mann-Whitney U-test and X2-test and adjusted analyses with General Linear Models and logistic/ordinal logistic regression. Results A total of 305 IA patients were included (167 men, 138 women). A significantly lower proportion of women (45%) than men (59%) were in remission according to disease-specific composite scores (p = 0.02). Women had significantly worse scores on pain, joint pain, fatigue, enthesitis, Health Assessment Questionnaire and Short Form (SF)-36 vitality and social functioning (all p≤0.04). Both sexes had worse SF-36 scale scores than the general population. Women reported more absenteeism (work time missed) and activity impairment. TNFi trough levels, neutralizing antibodies and calprotectin were similar across sexes. A similar total number of comorbidities was seen. Self-reported hypothyroidism was more frequent in women. Men had higher 10-year calculated risk of fatal cardiovascular events. Conclusion Important differences in disease burden between men and women were seen. More attention to sex differences in the follow-up of IA patients is warranted.
Wideband turnstile junction coaxial waveguide orthomode transducer

A wideband turnstile junction coaxial waveguide orthomode transducer (OMT) is presented in this paper, featuring coaxial waveguide input and orthogonal rectangular waveguide outputs. It primarily comprises of a turnstile junction, bending stepped impedance transformers and power combiners. The symmetrical geometry helps achieve wide operating bandwidth and balanced output phases. The OMT covers the whole Ku band from 12 to 18 GHz, which aims at wideband dual‐polarized signal combination and separation within coaxial‐type multi‐band antenna systems. An experimental prototype is manufactured and the measured results confirm that the reflection coefficient is lower than −15 dB within the whole band, and the port isolation is better than 35 dB. Turnstile junction coaxial waveguide OMTs can be adopted widely in circular/coaxial waveguide hybrid feeding networks for multi‐band satellite communication/remote sensing antenna systems.
PlexinA1 activation induced by β2-AR promotes epithelial-mesenchymal transition through JAK-STAT3 signaling in human gastric cancer cells

With the medical model shifting from a single biomedical model to a biopsychological-social model, the impact of psychosocial factors on cancer patients has attracted attention. Studies have shown that chronic stress caused by long-term psychological stress, such as anxiety and depression, can promote the malignant progression of tumors by acting on β2-adrenergic receptor (β2-AR). β2-AR can promote tumor migration by activating epithelial-mesenchymal transition (EMT). However, the underlying mechanisms in the regulation of EMT by β2-AR are still unclear. In this study, we established a chronic stress model by treating MGC-803 and SGC-7901 human gastric cancer cells with isoproterenol (ISO), a β2-AR agonist. EMT in the two gastric cancer cell lines was enhanced after ISO treatment. Thereafter, we found that the interaction between β2-AR and PlexinA1 was involved in the process by which chronic stress affects EMT in both MGC-803 and SGC-7901 cells. Moreover, the activation of β2-AR by ISO increased the expression of PlexinA1, activated JAK-STAT3 signaling and further promoted EMT in human gastric cancer cells. Importantly, the knockdown of PlexinA1 by small hairpin RNAs inhibited JAK-STAT3 signaling and abolished the EMT induced by β2-AR. In conclusion, PlexinA1 was an important downstream target of β2-AR, through which β2-AR promoted EMT in human gastric cancer cells by activating JAK-STAT3 signaling.