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Abstract Drosophila suzukii lay eggs in soft-skinned, ripening fruits, making this insect a serious threat to berry production. Since its 2008 introduction into North America, growers have used insecticides, such as pyrethroids and spinosads, as the primary approach for D. suzukii management, resulting in development of insecticide resistance in this pest. This study sought to identify the molecular mechanisms conferring insecticide resistance in these populations. We sequenced the transcriptomes of two pyrethroid- and two spinosad-resistant isofemale lines. In both pyrethroid-resistant lines and one spinosad-resistant line, we identified overexpression of metabolic genes that are implicated in resistance in other insect pests. In the other spinosad-resistant line, we observed an overexpression of cuticular genes that have been linked to resistance. Our findings enabled the development of molecular diagnostics that we used to confirm persistence of insecticide resistance in California, U.S.A. To validate these findings, we leveraged D. melanogaster mutants with reduced expression of metabolic or cuticular genes that were found to be upregulated in resistant D. suzukii to demonstrate that these genes are involved in promoting resistance. This study is the first to characterize the molecular mechanisms of insecticide resistance in D. suzukii and provides insights into how current management practices can be optimized.

The impact of long-term services and supports on the quality of life of adults with intellectual and developmental disabilities (IDD) is not well understood given the highly complex nature of researching this topic. To support future research addressing this topic, we conducted a systematic literature review of studies addressing outcomes of adults with IDD receiving long-term services and supports. Results of this review describe current outcomes for adults with IDD who receive long-term services and supports and can be used to inform program evaluation, policy development, and future research.

This article shares the results from a quasi-experimental mixed-methods study of a promising transition-focused professional development approach. The 12-week team-based intervention resulted in positive outcomes among intervention group participants' knowledge and capacities. The intervention group exhibited statistically significant changes in knowledge of transition assessment practices as well as in using various types of age-appropriate transition assessments and implementing effective practices associated with a comprehensive transition assessment process. At the program level, findings indicated team-level indicators showed statistically significant improvements. The study demonstrated teams who received the intervention were more likely to attain a program-level goal, which was substantially greater than the comparison teams. Implications for future research and practice are shared.

In this article, we describe the conceptualization and development of the Secondary Transition Fidelity Assessment (STFA), a measure intended for use by high school leadership teams to examine secondary programs and practices demonstrated by research to lead to meaningful outcomes for secondary students with and without disabilities. We describe our conceptualization and development efforts, which resulted in a measure with six critical features: adolescent engagement, district-level capacity, school-level capacity, community engagement, family engagement, and professional capacity. Based on stakeholder feedback, we revised the STFA and developed an instruction manual and action planning guide to support the self-evaluation of secondary programs and practices using data from the STFA. Recommendations for the field related to research, policy, and practice are provided.

All lineages of SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, contain mutations between amino acids 199 and 205 in the nucleocapsid (N) protein that are associated with increased infectivity. The effects of these mutations have been difficult to determine because N protein contributes to both viral replication and viral particle assembly during infection. Here, we used single-cycle infection and virus-like particle assays to show that N protein phosphorylation has opposing effects on viral assembly and genome replication. Ancestral SARS-CoV-2 N protein is densely phosphorylated, leading to higher levels of genome replication but 10-fold lower particle assembly compared to evolved variants with low N protein phosphorylation, such as Delta (N:R203M), Iota (N:S202R), and B.1.2 (N:P199L). A new open reading frame encoding a truncated N protein called N*, which occurs in the B.1.1 lineage and subsequent lineages of the Alpha, Gamma, and Omicron variants, supports high levels of both assembly and replication. Our findings help explain the enhanced fitness of viral variants of concern and a potential avenue for continued viral selection.

Background/Objectives: There is potential utility and increasing interest in engaging professionals in non-traditional vaccination settings to participate in efforts to reduce human papillomavirus (HPV)-related cancer. This study assessed the impact of a multi-disciplinary HPV educational intervention on oral health care professionals’ perceived role, comfort level, and scope of practice in HPV-related cancer prevention efforts. Methods: The virtual educational intervention was provided by a multi-disciplinary panel of experts. Seventy-three oral health care professionals attended the educational intervention and completed a questionnaire at three time points (pre-session, immediate post-session, and at the 1-month follow-up). Data were analyzed using Friedman’s ANOVA and post-hoc analyses. Results: Respondent’s median belief that it is the role of an oral health professional to recommend the HPV vaccine increased from pre-session (Median = 3.0, IQR = 3.0–4.0) to immediate post-session (median = 4.5, IQR = 4.0–5.0), and this increase was maintained 1 month after the session (median = 4.0, IQR = 4.0–4.5; p < 0.001). Additionally, respondent’s belief that they were up-to-date on the latest guidelines for HPV vaccination also increased from pre-session to immediate post-session (p < 0.05), and this increase was maintained 1 month after the session (pre-session median = 2.0, IQR = 2.0–3.0 vs. 1-month post-session median = 4.0, IQR = 4.0–5.0; p < 0.005). Conclusions: The multi-disciplinary HPV educational intervention was well-received by oral health professionals. Data suggest the intervention had a lasting impact on their beliefs about their role, comfort level, and scope of practice relating to HPV cancer prevention. More research needs to be conducted to better understand how obstetrician-gynecologists, other obstetric care providers, and oral health communities can support each other in promoting HPV-related cancer prevention.

Carrot motley dwarf (CMD) is a viral disease complex caused by co-infection of the polerovirus carrot red leaf virus with the umbraviruses carrot mottle virus or carrot mottle mimic virus, and/or a tombusvirus like associated RNA (tlaRNA), which depend on co-infection with a helper polerovirus to gain aphid transmissibility. In 2020 and 2021 carrot samples from Washington, United States (U.S.), and parsley and cilantro samples from California, U.S., exhibiting typical symptoms of CMD were submitted for diagnosis. Initial RT-PCR diagnostic assays identified the typical CMD viruses in the carrot samples, however only the umbraviruses and tlaRNAs were detected in the parsley and cilantro samples; as such, these samples were retested with another RT-PCR assay for generic polerovirus detection. Unexpectedly, the poleroviruses Torilis crimson leaf virus (TorCLV) and fennel motley virus were identified. Subsequent RNA sequencing analysis was conducted to confirm these results and look for other emergent viruses. In addition to confirming the diagnostic results, the recently described polerovirus Foeniculum vulgare polerovirus, the umbraviruses Pastinaca umbravirus 1 and wild carrot mottle virus, and the tlaRNA Arracacha latent virus E associated RNA were identified, making this the first report of these viruses and tlaRNA in the U.S. Using phylogenetic and pairwise identity comparisons and RDP4 recombination analyses, we also identified a putative novel polerovirus, for which we propose the name parsley polerovirus, that appears to be a recombinant between carrot polerovirus 1, sharing 92% amino acid (aa) identity with the RNA dependent RNA polymerase in the 5′ gene block, and TorCLV, sharing >98% aa identity with the capsid protein in the 3 gene block. This work adds to the growing list of polerovirus species exhibiting recombination between the 5′ and 3′ gene blocks, and highlights the unique, variable, and dynamic associations that can occur in polerovirus, umbravirus, and tlaRNA disease complexes.

The insect gustatory receptors (Grs) are one of the largest families of ion channels in the animal kingdom. Frank et al.1 unveil the structure of a fructose-sensing Gr and provide insight into its function.

BackgroundHigh-altitude populations exhibit distinct cellular, respiratory, and cardiovascular phenotypes, some of which provide adaptive advantages to hypoxic conditions compared to populations with sea-level ancestry. Studies performed in populations with a history of high-altitude residence, such as Tibetans, support the idea that many of these phenotypes may be shaped by genomic features that have been positively selected for throughout generations. We hypothesize that such traits observed in Tibetans at high altitude also occur in Tibetans living at intermediate altitude, even in the absence of severe sustained hypoxia.MethodologyWe studied individuals of high-altitude ancestry (Tibetans, n = 17 females; n = 12 males) and sea-level ancestry (Han Chinese, n = 6 females; n = 10 males), both who had been living at ∼1300 m (∼4327 ft) for at least 18 months. We measured hemoglobin concentration ([Hb]), hypoxic ventilatory response (HVR), and hypoxic heart rate response (HHRR) with end-tidal CO2 (PetCO2) held constant (isocapnia) or allowed to decrease with hypoxic hyperventilation (poikilocapnia). We also quantified the contribution of CO2 on ventilation and heart rate by calculating the differences of isocapnic versus poikilocapnic hypoxic conditions (Δ V˙I/ΔPetCO2 and ΔHR/ΔPetCO2, respectively).ResultsMale Tibetans had lower [Hb] compared to Han Chinese males (p < 0.05), consistent with reports for individuals from these populations living at high altitude and sea level. Measurements of ventilation (resting ventilation, HVR, and PetCO2) were similar for both groups. Heart rate responses to hypoxia were similar in both groups during isocapnia; however, HHRR in poikilocapnia was reduced in the Tibetan group (p < 0.03), and the heart rate response to CO2 in hypoxia was lower in Tibetans relative to Han Chinese (p < 0.01).ConclusionThese results suggest that Tibetans living at intermediate altitude have blunted cardiac responses in the context of hypoxia. Hence, only some of the phenotypes observed in Tibetans living at high altitude are observed in Tibetans living at intermediate altitude. Whereas blunted cardiac responses to hypoxia is revealed at intermediate altitudes, manifestation of other physiological adaptations to high altitude may require exposure to more severe levels of hypoxia.

Abstract Current treatments for T cell malignancies encounter issues of disease relapse and off-target toxicity. Using T cell receptor (TCR)Vβ2 as a model, here we demonstrate the rapid generation of an off-the-shelf allogeneic chimeric antigen receptor (CAR)-T platform targeting the clone-specific TCR Vβ chain for malignant T cell killing while limiting normal cell destruction. Healthy donor T cells undergo CRISPR-induced TRAC, B2M and CIITA knockout to eliminate T cell-dependent graft-versus-host and host-versus-graft reactivity. Second generation 4-1BB/CD3zeta CAR containing high affinity humanized anti-Vβ scFv is expressed efficiently on donor T cells via both lentivirus and adeno-associated virus transduction with limited detectable pre-existing immunoreactivity. Our optimized CAR-T cells demonstrate specific and persistent killing of Vβ2+ Jurkat cells and Vβ2+ patient derived malignant T cells, in vitro and in vivo, without affecting normal T cells. In parallel, we generate humanized anti-Vβ2 antibody with enhanced antibody-dependent cellular cytotoxicity (ADCC) by Fc-engineering for NK cell ADCC therapy.

Background: Cementless metaphyseal filling stems rely on fixation in the medial-to-lateral and anterior-to-posterior (AP) planes. The purpose of this preclinical study was to develop Insignia, a new metaphyseal filling system to match the anatomy of the proximal femur, and then compare it to clinically successful stems in multiple simulations. Methods: In this preclinical study, the geometry of the proximal femur in the AP plane among 1321 healthy subjects was evaluated using computed tomography. This data was then used to design insignia. Preclinical studies were performed to compare the broaching effort required to prepare a canal using this system, assess the reliability of seating heights for the stem, and compare in vitro micromotion testing of the stem under simulated stair climb activity. Results: The proximal femur decreased approximately 50% in the AP plane spanning 20 mm above the lesser trochanter to 30 mm below the lesser trochanter. Additional bench top testing was performed, and the new stem system was found to demonstrate significantly reduced broaching effort (average 6 vs 29 hits, P-value = .000), reliable seating heights on stem placement, and 70% less proximal micromotion on 10,000-cyclic testing (P < .05) compared to another clinically successful metaphyseal filling stem. Conclusions: The AP dimension of the proximal femur decreases nearly 50% throughout its length. Metaphyseal filling stems that match the AP anatomy of the proximal femur may require fewer hits during broaching, yield reproducible seating heights, and reduce micromotion on cyclic testing.

Microresonator frequency combs and their design versatility have revolutionized research areas from data communication to exoplanet searches. While microcombs in the 1550 nm band are well documented, there is interest in using microcombs in other bands. Here, we demonstrate the formation and spectral control of normal-dispersion dark soliton microcombs at 1064 nm. We generate 200 GHz repetition rate microcombs by inducing a photonic bandgap of the microresonator mode for the pump laser with a photonic crystal. We perform the experiments with normal-dispersion microresonators made from Ta2O5 and explore unique soliton pulse shapes and operating behaviors. By adjusting the resonator dispersion through its nanostructured geometry, we demonstrate control over the spectral bandwidth of these combs, and we employ numerical modeling to understand their existence range. Our results highlight how photonic design enables microcomb spectra tailoring across wide wavelength ranges, offering potential in bioimaging, spectroscopy, and photonic-atomic quantum technologies.

Abstract Background Intervertebral disc herniation (IVDH) is one of the most common causes of spinal cord injury (SCI) in dogs. As a result of acute SCI, a complex inflammatory response occurs in the spinal cord. Th17 cells (Th17) produce pro-inflammatory cytokines, while regulatory T cells (Treg) have opposite effects producing anti-inflammatory cytokines. Therefore, the aim of this study was to determine whether Th17- and Treg cells are involved in the pathogenesis of SCI or whether cellular changes occur due to coexisting inflammatory diseases. We hypothesized that chronic alterations in the Th17/Treg ratio are associated with a worse outcome after SCI. Methods Twenty-six paretic or plegic dogs with IVDH with and without coexisting inflammatory disease were investigated in the acute stage of the disease and after recovery of SCI. In addition, a healthy control group was included (n = 14). Quantification of Th17 and Treg cells, from peripheral blood samples, was performed by multicolor flow cytometry and IL17 was measured using an enzyme-linked immunosorbent assay (ELISA). Results After recovery significantly higher levels of Th17 (p = 0.0265) and Treg cells (p = 0.00025) were detected compared to acute IVDH but Th17/Treg ratio did not differ significantly. Recovered dogs and the control group did not differ significantly from each other. No association between an imbalance in the ratio and neurologic severity or underlying inflammatory diseases was found. Conclusion This study demonstrated that altered Th17 and Treg levels in peripheral blood are altered in the acute stage of IVDH, preexisting inflammatory diseases seem not to influence these cell populations. Th17 and Treg cells could be considered when evaluating new treatment strategies for SCI.

Research data sharing has become an expected component of scientific research and scholarly publishing practice over the last few decades, due in part to requirements for federally funded research. As part of a larger effort to better understand the workflows and costs of public access to research data, this project conducted a high-level analysis of where academic research data is most frequently shared. To do this, we leveraged the DataCite and Crossref application programming interfaces (APIs) in search of Publisher field elements demonstrating which data repositories were utilized by researchers from six academic research institutions between 2012-2022. In addition, we also ran a preliminary analysis of the quality of the metadata associated with these published datasets, comparing the extent to which information was missing from metadata fields deemed important for public access to research data. Results show that the top 10 publishers accounted for 89.0% to 99.8% of the datasets connected with the institutions in our study. Known data repositories, including institutional data repositories hosted by those institutions, were initially lacking from our sample due to varying metadata standards and practices. We conclude that the metadata quality landscape for published research datasets is uneven; key information, such as author affiliation, is often incomplete or missing from source data repositories and aggregators. To enhance the findability, interoperability, accessibility, and reusability (FAIRness) of research data, we provide a set of concrete recommendations that repositories and data authors can take to improve scholarly metadata associated with shared datasets.

[This corrects the article DOI: 10.1371/journal.pone.0302426.].

Frequency combs with mode spacing of 10–20 GHz are critical for increasingly important applications such as astronomical spectrograph calibration, high-speed dual-comb spectroscopy, and low-noise microwave generation. While electro-optic modulators and microresonators can provide narrowband comb sources at this repetition rate, a significant remaining challenge is a means to produce pulses with sufficient peak power to initiate nonlinear supercontinuum generation spanning hundreds of terahertz (THz) as required for self-referencing. Here, we provide a simple, robust, and universal solution to this problem using off-the-shelf polarization-maintaining amplification and nonlinear fiber components. This fiber-integrated approach for nonlinear temporal compression and supercontinuum generation is demonstrated with a resonant electro-optic frequency comb at 1550 nm. We show how to readily achieve pulses shorter than 60 fs at a repetition rate of 20 GHz. The same technique can be applied to picosecond pulses at 10 GHz to demonstrate temporal compression by 9× and achieve 50 fs pulses with a peak power of 5.5 kW. These compressed pulses enable flat supercontinuum generation spanning more than 600 nm after propagation through multi-segment dispersion-tailored anomalous-dispersion highly nonlinear fibers or tantala waveguides. The same 10 GHz source can readily achieve an octave-spanning spectrum for self-referencing in dispersion-engineered silicon nitride waveguides. This simple all-fiber approach to nonlinear spectral broadening fills a critical gap for transforming any narrowband 10–20 GHz frequency comb into a broadband spectrum for a wide range of applications that benefit from the high pulse rate and require access to the individual comb modes.

The authors demonstrate a multi-dimensional communication scheme that combines wavelength- and mode- multiplexing on photonic integrated circuits using foundry-compatible photonic inverse design and spectrally flattened microcombs

Abstract Turbidity monitoring in shallow coastal waters is fundamental to marine ecosystem research, management and protection. Satellite‐based water turbidity monitoring can be conducted at a greater spatial extent and higher temporal frequency than field measurements. The new Planet Dove satellite constellation has a daily revisit frequency and higher spatial resolution than Sentinel or Landsat satellites, allowing Planet Dove to track water turbidity dynamics in greater detail when suitable atmospheric correction is provided. We developed a new shallow coastal water turbidity estimation algorithm for Planet Dove and similar multi‐spectral satellites. Our algorithm accounts for bottom reflectance in total water‐leaving radiance to derive turbidity values in shallow coastal waters. We tested the algorithm with data from 235 Dove satellite images at five sites with different water conditions (Pelekane Bay, Big Island, Hawai‘i; Hilo Bay, Big Island, Hawai‘i; Kilo Nalu and Ala Wai, O‘ahu, Hawai‘i; Fagatele Bay, American Samoa; Vieques Island, Puerto Rico). We then validated satellite‐derived turbidity results (RMSE = 0.79–1.12 FNU [Formazin Nephelometric Unit]) using 75 days of field‐measured data, ranging in turbidity from 0.1 to 11.6 FNU in the five sites. Results show that our algorithm accurately detects turbidity in critical nearshore environments. In Hawai‘i, we used ~6700 Dove images to support a weekly turbidity monitoring study at a large geographic scale. We found this new, shallow‐water algorithm can be effectively applied to Dove satellite data to monitor water turbidity at high temporal resolution.

Understanding how temperature affects coral reef fish recruitment success is crucial for assessing impacts of ocean warming on coral reef resilience. We utilized a long-term fish survey dataset along the west coast of Hawai‘i Island to investigate the role of sea surface temperature (SST) in influencing recruitment timing and density. The dataset consisted of 17 years of surveys, with 25 sites annually surveyed in the months of May, July, September and November. We found that peak recruitment, i.e. the maximum number of recruits recorded across all surveys per year, usually occurred during July surveys. For sites where peak recruitment for that year occurred outside July, there were significantly fewer fish recruits than for sites whose peak recruitment occurred in July. In addition, the timing of peak recruitment is influenced by anomalously warm or cool years prior to spawning. The decrease in recruit density outside these times is likely influenced by recruits being exposed to temperatures warmer and cooler than their optimum. Our results show that climate variability is having an impact on the timing of peak recruitment, creating a mismatch between the thermal optimum of developing recruits and the thermal environment they develop in, negatively affecting recruit density in critical coral reef habitats. Altered and reduced recruitment has the potential to disrupt reef community structure and long-term fisheries sustainability in Hawai‘i, with important management implications for coral reefs in the future.

Rodent models are useful for understanding the mechanisms that underlie opioid addiction, but most preclinical studies have focused on rewarding and consummatory aspects of opioids without components of dependence-induced escalation of drug taking or seeking. We characterized several opioid-related behaviors in mice using a model of vaporized fentanyl self-administration. Male and female C57BL/6J mice were assigned to short-access (ShA; 1 h, nondependent) or long-access (LgA; 6 h, dependent) fentanyl vapor self-administration and subsequently tested in a battery of behavioral tests, followed by blood collection during withdrawal. Compared with mice in the ShA group, mice in the LgA group escalated their fentanyl intake, were more motivated to work to obtain the drug, exhibited greater hyperalgesia, and exhibited greater signs of naloxone-precipitated withdrawal. Principal component analysis indicated the emergence of two independent behavioral constructs: “intake/motivation” and “hyperalgesia/punished seeking.” In mice in the LgA condition only, “hyperalgesia/punished seeking” was associated with plasma levels of proinflammatory interleukin-17 (IL-17), chemokine (C-C motif) ligand 4 (CCL-4), and tumor necrosis factor α (TNF-α). Overall, the results suggest that extended access to opioids leads to addiction-like behavior, and some constructs that are associated with addiction-like behavior may be associated with levels of the proinflammatory cytokines/chemokines IL-17, TNF-α, and CCL-4 in blood.

Abstract Wildfires and housing development have increased since the 1990s, presenting unique challenges for wildfire management. However, it is unclear how the relative influences of housing growth and changing wildfire occurrence have altered risk to homes, or the potential for wildfire to threaten homes. We used a random forests model to predict burn probability in relation to weather variables at 1‐km resolution and monthly intervals from 1990 through 2019 in the Southern Rocky Mountains ecoregion. We quantified risk by combining the predicted burn probabilities with decadal housing density. We then compared the predicted burn probabilities and risk across the study area with observed values and quantified trends. Finally, we evaluated how housing growth and changes in burn probability influenced risk individually and combined. Fires burned 9055 km2 and exposed more than 8500 homes from 1990 to 2019. Observed burned area increased 632% from the 1990s to the 2000s, which combined with housing growth, resulted in a 1342% increase in homes exposed. Increases continued in the 2010s but at lower rates; burned area by 65% and exposure by 32%. The random forests model had excellent fit and high correlation with observations (AUC = 0.88 and r = 0.9). Observed values were within the 95% uncertainty interval for all years except 2016 (burned area) and 2000 (exposure). However, our model overpredicted in years with low observed burned area and underpredicted in years with high observed burned area. Overpredictions in risk resulted in lower rates of change in predicted risk compared with change in observed exposure. Increases in risk between the 1990s and 2000s were primarily due to warmer and drier weather conditions and secondarily because of housing growth. However, increases between the 2000s and 2010s were primarily due to housing growth. Our modeling approach identifies spatial and temporal patterns of wildfire potential and risk, which is critical information to guide decision‐making. Because the drivers behind risk shift over time, strategies to mitigate risk may need to account for multiple drivers simultaneously.

Introduction: Aircrew may experience rapidly oscillating inspired O2/N2 ratios owing to fluctuations in the on-board oxygen delivery systems (OBOG). Recent investigations suggest these oscillations may contribute to the constellation of physiologic events in aircrew of high-performance aircraft. Therefore, the purpose of this study was to determine whether these “operationally-relevant” environmental challenges may cause decrements in measures of pulmonary vascular physiology.Methods: Thirty healthy participants (Age: 29 ± 5 years) were recruited and assigned to one of the three exposures. Participants were instrumented for physiologic monitoring and underwent baseline cardiopulmonary physiology testing (ground level) consisting of a rebreathe method for quantifying pulmonary blood flow (Qc), pulmonary capillary blood volume (Vc) and alveolar–capillary conductance (Dm). Ultrasound was used to quantify “comet tails” (measure of lung fluid balance). After baseline testing, the participants had two 45 min exposures to an altitude of 8,000 ft where they breathed from gas mixtures alternating between 80/20 and 30/70 O2/N2 ratios at the required frequency (30 s, 60 s, or 120 s), separated by repeat baseline measure. Immediately and 45 min after the second exposure, baseline measures were repeated.Results: We observed no changes in Qc, Dm or Vc during the 60 s exposures. In response to the 30 s oscillation exposure, there was a significantly reduced Qc and Vc at the post-testing period (p = 0.03). Additionally, exposure to the 120 s oscillations resulted in a significant decrease in Vc at the recovery testing period and an increase in the Dm/Vc ratio at both the post and recovery period (p < 0.01). Additionally, we observed no changes in the number of comet tails.Conclusion: These data suggest “operationally-relevant” changes in inspired gas concentrations may cause an acute, albeit mild pulmonary vascular derecruitment, reduced distention and/or mild pulmonary-capillary vasoconstriction, without significant changes in lung fluid balance or respiratory gas exchange. The operational relevance remains less clear, particularly in the setting of additional environmental stressors common during flight (e.g., g forces).

Carotid body paragangliomas are the most common extra-adrenal paraganglioma and arise from the carotid body at the bifurcation of the internal carotid artery and external carotid artery. The differential diagnosis for a cervical mass in this region includes vagal paraganglioma, jugulotympanic paraganglioma, middle ear adenoma, meningioma, schwannoma, and thyroid malignancy. This case describes an otherwise healthy 23 year old female who presented with right neck pain, swelling, difficulty swallowing, and intermittent left arm weakness and numbness. Multiple imaging studies demonstrated an 8 cm enhancing soft tissue mass encasing the internal carotid artery and extending from the carotid bifurcation to the skull base, with intracranial involvement of the posterior fossa. Due to the tumor location as well as involvement of the carotid artery, a multi-disciplinary team consisting of oral and maxillofacial surgery and vascular surgery performed resection of the tumor utilizing exposure of the skull base with a double mandibular osteotomy technique. Though the presumptive diagnosis of the tumor was paraganglioma, the pathology report revealed the tumor was a psammomatous meningioma.Extracranial meningioma is a rare disease process. In this case there were several findings atypical for carotid body tumor or paraganglioma. Despite the enhancing features of the tumor on CT scan there was no splaying of the internal and external carotid arteries that would be typical for a carotid body tumor. Moreover, though the majority of the tumor mass was extracranial, there was intracranial extension which is rare for cervical paragangliomas. With imaging showing tumor encasement of the carotid artery, preoperative planning was assisted by a ‘halo sign’ that demonstrated a tissue plane between the mass and the internal carotid artery (Figure). This case demonstrates the importance of establishing a wide differential diagnosis for a cervical mass and highlights that an extracranial meningioma can mimic a cervical paraganglioma. The creation of a multidisciplinary team proved essential for effective access to tumor removal and patient safety.

The agricultural pest Drosophila suzukii differs from most other Drosophila species in that it lays eggs in ripe, rather than overripe, fruit. Previously, we showed that changes in bitter taste sensation accompanied this adaptation (Dweck et al., 2021). Here, we show that D. suzukii has also undergone a variety of changes in sweet taste sensation. D. suzukii has a weaker preference than Drosophila melanogaster for laying eggs on substrates containing all three primary fruit sugars: sucrose, fructose, and glucose. Major subsets of D. suzukii taste sensilla have lost electrophysiological responses to sugars. Expression of several key sugar receptor genes is reduced in the taste organs of D. suzukii. By contrast, certain mechanosensory channel genes, including no mechanoreceptor potential C, are expressed at higher levels in the taste organs of D. suzukii, which has a higher preference for stiff substrates. Finally, we find that D. suzukii responds differently from D. melanogaster to combinations of sweet and mechanosensory cues. Thus, the two species differ in sweet sensation, mechanosensation, and their integration, which are all likely to contribute to the differences in their egg-laying preferences in nature.

A stress adaptation pathway termed the integrated stress response has been suggested to be active in many cancers including prostate cancer (PCa). Here, we demonstrate that the eIF2 kinase GCN2 is required for sustained growth in androgen-sensitive and castration-resistant models of PCa both in vitro and in vivo, and is active in PCa patient samples. Using RNA-seq transcriptome analysis and a CRISPR-based phenotypic screen, GCN2 was shown to regulate expression of over 60 solute-carrier (SLC) genes, including those involved in amino acid transport and loss of GCN2 function reduces amino acid import and levels. Addition of essential amino acids or expression of 4F2 (SLC3A2) partially restored growth following loss of GCN2, suggesting that GCN2 targeting of SLC transporters is required for amino acid homeostasis needed to sustain tumor growth. A small molecule inhibitor of GCN2 showed robust in vivo efficacy in androgen-sensitive and castration-resistant mouse models of PCa, supporting its therapeutic potential for the treatment of PCa.

Turbidity from land-based runoff has been identified as a possible driver of coral bleaching refugia, as particulate matter in turbid habitats may block excessive irradiance and alter the food supply to corals during ocean heatwaves. However, negative effects of turbidity have also been documented worldwide, and high-resolution data across reef regions are required to identify habitats where turbidity is harmful or helpful during heatwaves. We monitored turbidity across five Main Hawaiian Islands during a 2019 ocean heatwave using Planet Dove satellites (3.7 m spatial resolution, extracted at 100 m resolution) to examine relationships between turbidity and coral bleaching occurrence and severity. We also attributed turbidity to urban and non-urban land uses to determine how turbidity associated with different human activities affects coral bleaching. We found that, while turbidity had a negative relationship with coral bleaching severity, this effect weakened at higher temperatures, especially in rural areas. However, turbidity maintained a slightly negative effect on bleaching severity in urban settings. In addition, while thermal stress was the predominant driver of bleaching occurrence, interactions between temperature and local variables like turbidity and wave energy were the most significant drivers of bleaching severity. This study represents one of the first high-resolution analyses of turbid refugia at large spatial scales. We show how new data sources from remote sensing can provide scalable yet context-specific information to coastal managers addressing land-sea runoff.

Nonlinear wavelength conversion is a powerful control of light, especially when implemented at the nanoscale with integrated photonics. However, strict energy conservation and phase-matching requirements constrain the converted output. To overcome these constraints and enable novel functionalities, we introduce nonlinear networks—systems of nonlinear photonic elements that observe a programmable set of conservation rules. We highlight the diverse capabilities of nonlinear networks by demonstrating an optical-frequency synthesizer, which operates at nearly arbitrary output frequency exceeding the state of the art in synthesized conversion bandwidth. Using a codesigned microresonator network, our synthesizer is based on four-wave mixing (FWM) spectral translation of a tunable laser and a frequency comb. Energy conservation in FWM provides deterministic synthesis, and it allows a nearly arbitrary frequency tuning range by the dependence of resonant FWM on group-velocity dispersion, temperature, and input laser frequency. Moreover, we take advantage of efficient parametric amplification intrinsic to nonlinear networks. We operate spectral translation across output ranges up to 200 THz, and we characterize the synthesizer through precise metrology, demonstrating

Parasitoids exploit host bodies for reproduction, selecting for host defences. A new host defence is reported, in which adult Drosophila accelerate mating behaviour at the sight of certain parasitoid wasps, mediated by the upregulation of a nervous system gene that encodes a 41-amino acid micropeptide.

Abstract Biofluorescence has been detected in several nocturnal-crepuscular organisms from invertebrates to birds and mammals. Biofluorescence in mammals has been detected across the phylogeny, including the monotreme duck-billed platypus (Ornithorhyncus anatinus), marsupial opossums (Didelphidae), and New World placental flying squirrels (Gluacomys spp.). Here, we document vivid biofluorescence of springhare (Pedetidae) in both museum specimens and captive individuals—the first documented biofluorescence of an Old World placental mammal. We explore the variation in biofluorescence across our sample and characterize its physical and chemical properties. The striking visual patterning and intensity of color shift was unique relative to biofluorescence found in other mammals. We establish that biofluorescence in springhare likely originates within the cuticle of the hair fiber and emanates, at least partially, from several fluorescent porphyrins and potentially one unassigned molecule absent from our standard porphyrin mixture. This discovery further supports the hypothesis that biofluorescence may be ecologically important for nocturnal-crepuscular mammals and suggests that it may be more broadly distributed throughout Mammalia than previously thought.

Abstract Background A core outcome set (COS) represents the agreed minimum set of domains and measurement instruments that should be measured and reported in any clinical trial for a given condition. In BMS randomized controlled trials (RCTs), the outcomes identified in the existing literature regarding the efficacy of therapeutic interventions are numerous and diverse. Although the standardized IMMPACT core outcome domains has been developed for measurement of outcomes in chronic pain RCTs, no BMS-specific COS have been adopted and validated. With the evolving landscape of BMS management end points and the development of new therapies, a consensus on a COS for use in future BMS trials is paramount to reduce heterogeneity in outcome reporting. The aim of this study was to reach a consensus for adopting the standardized Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) outcome domains, and their tools of assessment, for burning mouth syndrome (BMS) clinical trials and clinical practice. Methods A BMS-specific COS will be developed using the method recommended by the Core Outcome Measures in Effective Trials (COMET) initiative (Registration: http://www.comet-initiative.org/studies/details/1357 ). Selection of questionnaire outcome measures was informed by the IMMPACT consensus and previous systematic review of RCTs in BMS conducted by the consortium. An international group of clinicians and researchers will be invited to participate in several rounds of a Delphi survey. A consensus meeting will be held with the objective of ratifying the outcomes for inclusion in the COS. A finalized COS explanatory document will be drafted, including all outcomes and measurements as determined by the Delphi rounds and consensus meeting. Discussion A COS for the management of BMS will improve the quality of future RCTs, reduce outcome reporting heterogeneity, and facilitate more vigorous data synthesis of management interventions for systematic reviews and meta-analysis. This would ensure enhanced quality evidence for clinical management of the condition.

We identified a microRNA (miRNA) profile characterizing HIV lipodystrophy and explored the downstream mechanistic implications with respect to adipocyte biology and the associated clinical phenotype. miRNA profiles were extracted from small extracellular vesicles (sEVs) of HIV-infected individuals with and without lipodystrophic changes and individuals without HIV, among whom we previously showed significant reductions in adipose Dicer expression related to HIV. miR-20a-3p was increased and miR-324-5p and miR-186 were reduced in sEVs from HIV lipodystrophic individuals. Changes in these miRNAs correlated with adipose Dicer expression and clinical markers of lipodystrophy, including fat redistribution, insulin resistance, and hypertriglyceridemia. Human preadipocytes transfected with mimic miR-20a-3p, anti–miR-324-5p, or anti–miR-186 induced consistent changes in latent transforming growth factor beta binding protein 2 (Ltbp2), Wisp2, and Nebl expression. Knockdown of Ltbp2 downregulated markers of adipocyte differentiation (Fabp4, Pparγ, C/ebpa, Fasn, adiponectin, Glut4, CD36), and Lamin C, and increased expression of genes involved in inflammation (IL1β, IL6, and Ccl20). Our studies suggest a likely unique sEV miRNA signature related to dysregulation of Dicer in adipose tissue in HIV. Enhanced miR-20a-3p or depletion of miR-186 and miR-324-5p may downregulate Ltbp2 in HIV, leading to dysregulation in adipose differentiation and inflammation, which could contribute to acquired HIV lipodystrophy and associated metabolic and inflammatory perturbations.

Mangroves, seagrasses, and coral reefs interact in tropical regions throughout the world. These ecosystems exhibit strong synergies, as the health of each ecosystem supports the functioning of adjacent habitats. We present a global spatial analysis of mangrove, seagrass, and reef communities, identifying regions where these habitats co-occur. While only an estimated 18% of interaction zones are covered by protected areas, boundaries between mangroves, seagrasses, and reefs represent areas of high conservation efficiency, where benefits of conservation amplify synergistically as land-sea ecosystems are jointly managed. We discuss four types of conservation efficiencies in these coastal ecosystems: (1) increased resistance to disturbance through inter-ecosystem feedbacks, (2) high biodiversity within small geographic areas, (3) habitat portfolio effects giving rise to climate refugia, and (4) synergistic ecosystem services, where building one ecosystem service inherently increases others. Given these synergistic benefits, global campaigns to expand marine and terrestrial protection should focus on the tightly connective interface between mangroves, seagrasses, and reefs, in order to more efficiently build resilience within and between these habitats.

The successful treatment of prosthetic joint infection (PJI) is difficult, requiring coordination across multiple specialties. In 2017, we formed a collaboration between our infectious disease clinicians and our orthopaedic arthroplasty surgeons in an effort to optimize care, accommodate patients, and expedite clinical decision-making in the treatment of PJI. The model consisted of combined infectious disease and arthroplasty clinics, standardized lab results, and planned staged revision procedures. We named this the arthroplasty infection service. Our early experience with a defined multidisciplinary approach to PJI was positive. Although the impact of the arthroplasty infection service on PJI outcomes is yet to be determined, we believe this is a step forward in the management of this complex patient population. With an increasing burden of PJI in the United States, this model could be emulated at many institutions that regularly treat these challenging cases.

This essay argues that the proliferation of misogynistic hate speech during the 2016 U.S. presidential campaign had a dangerous chilling effect on womens free expression. The gendered slurs aimed at women candidates and journalists, both online and in-person, created a hostile political environment, which made it more difficult for women to fully participate in the process of Democratic self-governance. To address this issue, I recommend allocating state and federal tax dollars to counter speech efforts, and call for social media organizations, such as Facebook and Twitter, to reevaluate their hate speech and harassment policies. Keywords: Hate speech, 2016 U.S. presidential campaign, misogyny

Coral reefs are undergoing changes caused by coastal development, resource use, and climate change. The extent and rate of reef change demand robust and spatially explicit monitoring to support management and conservation decision-making. We developed and demonstrated an airborne-assisted approach to design and upscale field surveys of reef fish over an ecologically complex reef ecosystem along Hawai‘i Island. We also determined the minimal set of mapped variables, mapped reef strata, and field survey sites needed to meet three goals: (i) increase field survey efficiency, (ii) reduce field sampling costs, and (iii) ensure field sampling is geostatistically robust for upscaling to regional estimates of reef fish composition. Variability in reef habitat was best described by a combination of water depth, live coral and macroalgal cover, fine-scale reef rugosity, reef curvature, and latitude as a proxy for a regional climate-ecosystem gradient. In combination, these factors yielded 18 distinct reef habitats, or strata, throughout the study region, which subsequently required 117 field survey sites to quantify fish diversity and biomass with minimal uncertainty. The distribution of field sites was proportional to stratum size and the variation in benthic habitat properties within each stratum. Upscaled maps of reef survey data indicated that fish diversity is spatially more uniform than fish biomass, which was lowest in embayments and near land-based access points. Decreasing the number of field sites from 117 to 45 and 75 sites for diversity and biomass, respectively, resulted in a manageable increase of statistical uncertainty, but would still yield actionable trend data over time for the 60 km reef study region on Hawai‘i Island. Our findings suggest that high-resolution benthic mapping can be combined with stratified-random field sampling to generate spatially explicit estimates of fish diversity and biomass. Future expansions of the methodology can also incorporate temporal shifts in benthic composition to drive continuously evolving fish monitoring for sampling and upscaling. Doing so reduces field-based labor and costs while increasing the geostatistical power and ecological representativeness of field work.

Although opioids are potent analgesics, a consequence of chronic opioid use is hyperalgesia during withdrawal, which may contribute to opioid misuse. Dynorphin, the endogenous ligand of κ-opioid receptors (KORs), is upregulated in opioid-dependent rats and in animal models of chronic pain. However, the role of KORs in opioid withdrawal-induced hyperalgesia remains to be determined. We hypothesized that KOR antagonism would reverse opioid withdrawal-induced hyperalgesia in opioid-dependent rats. Male and female Wistar rats received daily injections of heroin (2–6 mg/kg, SC) and were tested for mechanical sensitivity in the electronic von Frey test 4–6 h into withdrawal. Female rats required significantly more heroin than male rats to reach comparable levels of both heroin-induced analgesia and hyperalgesia (6 mg/kg vs. 2 mg/kg). Once hyperalgesia was established, we tested the effects of the KOR antagonists nor-binaltorphimine (norBNI; 30 mg/kg, SC) and 5′-guanidinonaltrindole (5′GNTI; 30 mg/kg, SC). When the animals continued to receive their daily heroin treatment (or saline treatment in the repeated saline group) five times per week throughout the experiment, both KOR antagonists reversed heroin withdrawal-induced hyperalgesia. The anti-hyperalgesia effect of norBNI was more prolonged in males than in females (14 days vs. 7 days), whereas 5′GNTI had more prolonged effects in females than in males (14 days vs. 4 days). The behavioral effects of 5′GNTI coincided with higher 5′GNTI levels in the brain than in plasma when measured at 24 h, whereas 5′GNTI did not reverse hyperalgesia at 30 min posttreatment when 5′GNTI levels were higher in plasma than in the brain. Finally, we tested the effects of 5′GNTI on naloxone-induced and spontaneous signs of opioid withdrawal and found no effect in either male or female rats. These findings indicate a functional role for KORs in heroin withdrawal-induced hyperalgesia that is observed in rats of both sexes.

Summary:. Congenital sphenoid wing dysplasia is one of the major diagnostic criteria for neurofibromatosis type 1, and is often considered pathognomonic for the disease. Between 5% and 12% of neurofibromatosis type 1 cases have evidence of sphenoid wing dysplasia. Sequelae of this deficiency include slow expansion of the middle temporal fossa and progressive herniation of the temporal lobe into the orbital cavity, resulting in pulsatile exophthalmos. Herein, we report a patient with greater sphenoid wing agenesis and middle temporal fossa enlargement requiring transcranial orbital reconstruction in the absence of neurofibromatosis. To our knowledge, this represents a novel craniofacial phenotype of sphenoid wing agenesis in the absence of neurofibromatosis previously not described in the literature.

In mammals, HP1-mediated heterochromatin forms positionally and mechanically stable genomic domains even though the component HP1 paralogs, HP1α, HP1β, and HP1γ, display rapid on-off dynamics. Here, we investigate whether phase-separation by HP1 proteins can explain these biological observations. Using bulk and single-molecule methods, we show that, within phase-separated HP1α-DNA condensates, HP1α acts as a dynamic liquid, while compacted DNA molecules are constrained in local territories. These condensates are resistant to large forces yet can be readily dissolved by HP1β. Finally, we find that differences in each HP1 paralog’s DNA compaction and phase-separation properties arise from their respective disordered regions. Our findings suggest a generalizable model for genome organization in which a pool of weakly bound proteins collectively capitalize on the polymer properties of DNA to produce self-organizing domains that are simultaneously resistant to large forces at the mesoscale and susceptible to competition at the molecular scale.

Toxoplasma gondii

Although most Drosophila species lay eggs in overripe fruit, the agricultural pest Drosophila suzukii lays eggs in ripe fruit. We found that changes in bitter taste perception have accompanied this adaptation. We show that bitter-sensing mutants of Drosophila melanogaster undergo a shift in egg laying preference toward ripe fruit. D. suzukii has lost 20% of the bitter-sensing sensilla from the labellum, the major taste organ of the head. Physiological responses to various bitter compounds are lost. Responses to strawberry purées are lost from two classes of taste sensilla. Egg laying is not deterred by bitter compounds that deter other species. Profiling of labellar transcriptomes reveals reduced expression of several bitter Gr genes (gustatory receptors). These findings support a model in which bitter compounds in early ripening stages deter egg laying in most Drosophila species, but a loss of bitter response contributes to the adaptation of D. suzukii to ripe fruit.