Why do understorey Licuala palm fruits turn from red to white and then black when ripe?

Licuala ferruginea Becc., a tropical forest understorey palm, is observed to have fruits that appear red in colour when unripe, turning pink, then white, purple and finally black in colour as they ripen. We monitored 13 fruiting palms in rainforest fragments and recorded the consumption of fruits by animals via camera traps. We also documented the fruiting phenology of two palms in the nursery. In the rainforest fragments, a Cream-vented Bulbul (Pycnonotus simplex) was observed plucking a mature purple fruit from a L. ferruginea palm, before flying away with the fruit in its beak. This was the only bird that was observed feeding on the mature fruit. A range of mammals, dominated by edge species such as the Long-tailed Macaque and Wild Boar, were observed to consume L. ferruginea fruits indiscriminately across all five colour stages, thereby limiting the dispersal of the fruits. Forest bulbul gape sizes also matched the fruit size, suggesting that forest bulbuls are the likely dispersers of the palm in the original forest where edge species are not in high densities. We further posit that the initial phase of red fruits, with high contrasting red reflectance against a green foliage background, might be a form of early advertisement to birds. The fruit then turns pink and white, which have high green reflectance and is less contrasting, thereby reducing the conspicuity of the fruit. This allows the fruit to ripen with high fructose and glucose content, and turn purple and black, which are known visual cues for birds. This study provides indicative support for the dispersal syndrome hypothesis and highlights the potential effects of forest fragmentation on plant-frugivore interactions.

V-ToCs (Venom Toxin Clustering): A tool for the investigation of sequence and structure similarities in snake venom toxins.

Recently, there has been a major push toward the development of next-generation treatments against snakebite envenoming. However, unlike current antivenoms that rely on animal-derived polyclonal antibodies, most of these novel approaches are reliant on an in-depth understanding of the over 2000 known snake venom toxins. Indeed, by identifying similarities (i.e., conserved epitopes) across these different toxins, it is possible to design cross-reactive treatments, such as broadly-neutralising antibodies, that target these similarities. Therefore, in this project, we built an automated pipeline that generates sequence and structural distance matrices and homology trees across all available snake venom toxin sequences and structures. To facilitate analysis, we also developed a user-friendly and high-throughput visualisation tool, coined "Venom TOxin CluStering" (V-ToCs). This tool allows researchers to easily investigate sequence and structure patterns in snake venom toxins for a wide array of purposes, such as elucidating toxin evolution, and will also hopefully help guide the discovery and development of increasingly broadly-neutralising antivenoms in the near future.

Design and characterization of the time-resolved opacity spectrometer (OpSpecTR) for the NIF iron opacity campaign.

A new time-resolved opacity spectrometer (OpSpecTR) is currently under development for the National Ignition Facility (NIF) opacity campaign. The spectrometer utilizes Icarus version 2 (IV2) hybridized complementary metal-oxide-semiconductor sensors to collect gated data at the time of the opacity transmission signal, unlocking the ability to collect higher-temperature measurements on NIF. Experimental conditions to achieve higher temperatures are feasible; however, backgrounds will dominate the data collected by the current time-integrating opacity spectrometer. The shortest available OpSpecTR integration time of ∼2 ns is predicted to reduce self-emission and other late-time backgrounds by up to 80%. Initially, three Icarus sensors will be used to collect data in the self-emission, backlighter, and absorption regions of the transmission spectrum, with plans to upgrade to five Daedalus sensors in future implementations with integration times of ∼1.3 ns. We present the details of the diagnostic design along with recent characterization results of the IV2 sensors.

Resistance training improves cardiac function in older women: a randomized controlled trial.

This investigation aimed to determine the effects of 24 weeks of resistance training (RT) on cardiac function in older women. Seventy-three physically independent older women were selected for this investigation. Participants were randomized into a training group (TG, n = 38) and a control group (CG, n = 35). The RT program was conducted over 24 weeks and consisted of three sessions a week. Participants performed eight exercises for the whole body in three sets of 8-12 repetitions. Tissue Doppler echocardiography was performed, according to current guidelines, before and after 24 weeks of the intervention. One-repetition maximum (1-RM) tests were used to assess muscular strength. A group vs. time interaction (P < 0.05) was shown for left ventricular end-diastolic volume (TG = - 8.3% vs. CG = - 0.6%), left ventricular end-systolic volume (TG = - 10.6% vs. CG = + 1.1%), and left atrial volume index (TG = - 9.1% vs. CG = + 3.9%). A main time effect (P < 0.05) was found for left ventricular mass index (TG = + 4.9% vs. CG = - 0.6%), septal thickness (TG = + 3.3% vs. CG = - 1.7%), left ventricular ejection fraction (TG = + 3.7% vs. CG = - 0.5%), E'/E septal (TG = - 4.8% vs. CG = + 0.5%), deceleration time (TG = - 4.1% vs. CG = + 3.9%), E septal (TG = + 4.6% vs. CG = - 0.6%), and E lateral (TG = + 5.2% vs. CG = - 1.1%). These results suggest that 24 weeks of RT improves cardiac morphological and functional variables in older women.

Utility of ligamentum teres hepatis flap reinforcement to prevent postoperative pancreatic fistulas in robotic distal pancreatectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a significant contributor to morbidity and mortality after robotic distal pancreatectomy (RDP). Ligamentum teres hepatis (LTH) reinforcement of the pancreatic remnant may reduce the incidence of POPF. METHODS: Patients ≥18 years old, who underwent RDP at the University of Massachusetts Memorial Medical Center from 01/01/2018-08/31/2022. Primary endpoint was POPF incidence. Secondary outcomes included peri- and postoperative variables. RESULTS: Thirty-three patients underwent RDP, of which LTH reinforcement was used in 21 (64 â€‹%) cases. Six (18 â€‹%) patients developed a POPF. No association was identified between LTH flap reinforcement and POPF (OR 1.18, 95 â€‹% CI 0.18 to 7.85, p â€‹= â€‹0.87). There were no peri- or postoperative complications related to ligamentum teres flap creation. CONCLUSIONS: LTH reinforcement of the pancreatic remnant can be safely performed during RDP. Further studies are needed to assess the utility of this intervention to mitigate the risk of pancreatic fistula formation following RDP.

Speeding up the recovery of coastal habitats through management interventions that address constraints on dispersal and recruitment.

Plans for habitat restoration will benefit from predictions of timescales for recovery. Theoretical models have been a powerful tool for informing practical guidelines in planning marine protected areas, suggesting restoration planning could also benefit from a theoretical framework. We developed a model that can predict recovery times following restoration action, under dispersal, recruitment and connectivity constraints. We apply the model to a case study of seagrass restoration and find recovery times following restoration action can vary greatly, from <1 to >20 years. The model also shows how recovery can be accelerated when restoration actions are matched to the constraints on recovery. For example, spreading of propagules can be used when connectivity is the critical restriction. The recovery constraints we articulated mathematically also apply to the restoration of coral reefs, mangroves, saltmarsh, shellfish reefs and macroalgal forests, so our model provides a general framework for choosing restoration actions that accelerate coastal habitat recovery.

De novo designed proteins neutralize lethal snake venom toxins.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more1,2. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage3 and inhibition of nicotinic acetylcholine receptors (nAChRs) resulting in life-threatening neurotoxicity4. Currently, the only available treatments for snakebite consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs5,6,7. Here, we use deep learning methods to de novo design proteins to bind short- and long-chain α-neurotoxins and cytotoxins from the 3FTx family. With limited experimental screening, we obtain protein designs with remarkable thermal stability, high binding affinity, and near-atomic level agreement with the computational models. The designed proteins effectively neutralize all three 3FTx sub-families in vitro and protect mice from a lethal neurotoxin challenge. Such potent, stable, and readily manufacturable toxin-neutralizing proteins could provide the basis for safer, cost-effective, and widely accessible next-generation antivenom therapeutics. Beyond snakebite, our computational design methodology should help democratize therapeutic discovery, particularly in resource-limited settings, by substantially reducing costs and resource requirements for development of therapies to neglected tropical diseases.

Prospective Patient Preferences for Humor in Urologists Treating Erectile Dysfunction: A Survey Study.

INTRODUCTION: Men seeking treatment for sexual dysfunction can experience embarrassment as a result of stigma. This research manuscript presents the findings of a survey conducted to investigate the influence of humor on prospective patients' preferences when selecting a specialist to address erectile dysfunction (ED). METHODS: The respondents were presented with five pairs of mock urology business cards: one professional and one humorous. A questionnaire was designed and distributed via an online survey platform. Descriptive statistics and Fisher's exact test were performed using the Statistical Package for Social Sciences (SPSS) software version 29 (IBM SPSS Statistics, Armonk, NY) to evaluate age and race associations with card preference. RESULTS: Among the 997 participants, an average of 66.1% (a median of 71.2%) preferred professional cards. Humorous card selection rates ranged from 5.2% to 38.4% compared to 54.0% to 78.1% for professional cards. A statistically significant relationship between age and professional card choice existed in all except the fifth set of cards (p = 0.001, 0.001, 0.001, 0.001, and 0.054). The relationship between race or ethnicity and business card preference was not reported due to an imbalance in demographics, with most participants identifying as Caucasian. DISCUSSION: A humor-centric approach may not resonate with all individuals seeking treatment for sensitive conditions such as ED. Limitations include the subjectivity of humor, the use of an online survey platform, and the hypothetical nature of this study. Real patients experiencing ED may face stigma and respond to humor differently. CONCLUSION: This study provides insights into patient preference for professionalism over humor from their urologist but leaves room for the exploration of humor in medical contexts. Future studies could examine the impacts of humor on patient choices in real-world healthcare settings.

Early versus late penile prosthesis surgery: a cross-sectional real-life study unveiling predictive factors.

Penile prosthesis implantation (PP surgery) is a well-established solution for severe, medication-refractory erectile dysfunction (ED). Despite its effectiveness, limited data exists on patient characteristics influencing the timing of PP surgery after ED onset. We aimed to investigate predictors for early PP surgery and compare preoperative factors in men who had early (<12 months) vs. late PP surgery (≥12 months). We analyzed data from 210 men undergoing inflatable PP surgery for medication-refractory ED to investigate predictors for early PP surgery. Men with early PP surgery were older (64 vs. 61 years), had more comorbidities, (97.2% vs. 63.3% CCI ≥ 1). Linear regression analysis showed that more comorbidities were associated with an earlier time to PP surgery (Coeff: -1.82, 95% CI: -3.08 to -0.56, p = 0.004). At multivariate Cox regression analysis, CCI ≥ 1 emerged as the sole predictor of early PP surgery (OR: 1.29, 95% CI: 1.07-1.56, p = 0.007) after adjusting for age, ED etiology, and ethnicity. Our study sheds light on factors influencing decisions for early vs. late PP surgery post-medication-refractory ED. Men with more comorbidities were more likely to receive early PP surgery, emphasizing the importance of preoperative counseling and personalized treatment plans.

Deep-pelagic fishes: Demographic instability in a stable environment.

Demographic histories are frequently a product of the environment, as populations expand or contract in response to major environmental changes, often driven by changes in climate. Meso- and bathy-pelagic fishes inhabit some of the most temporally and spatially stable habitats on the planet. The stability of the deep-pelagic could make deep-pelagic fishes resistant to the demographic instability commonly reported in fish species inhabiting other marine habitats, however the demographic histories of deep-pelagic fishes are unknown. We reconstructed the historical demography of 11 species of deep-pelagic fishes using mitochondrial and nuclear DNA sequence data. We uncovered widespread evidence of population expansions in our study species, a counterintuitive result based on the nature of deep-pelagic ecosystems. Frequency-based methods detected potential demographic changes in nine species of fishes, while extended Bayesian skyline plots identified population expansions in four species. These results suggest that despite the relatively stable nature of the deep-pelagic environment, the fishes that reside here have likely been impacted by past changes in climate. Further investigation is necessary to better understand how deep-pelagic fishes, by far Earth's most abundant vertebrates, will respond to future climatic changes.

Stereo Camera Setup for 360° Digital Image Correlation to Reveal Smart Structures of Hakea Fruits.

About forty years after its first application, digital image correlation (DIC) has become an established method for measuring surface displacements and deformations of objects under stress. To date, DIC has been used in a variety of in vitro and in vivo studies to biomechanically characterise biological samples in order to reveal biomimetic principles. However, when surfaces of samples strongly deform or twist, they cannot be thoroughly traced. To overcome this challenge, different DIC setups have been developed to provide additional sensor perspectives and, thus, capture larger parts of an object's surface. Herein, we discuss current solutions for this multi-perspective DIC, and we present our own approach to a 360° DIC system based on a single stereo-camera setup. Using this setup, we are able to characterise the desiccation-driven opening mechanism of two woody Hakea fruits over their entire surfaces. Both the breaking mechanism and the actuation of the two valves in predominantly dead plant material are models for smart materials. Based on these results, an evaluation of the setup for 360° DIC regarding its use in deducing biomimetic principles is given. Furthermore, we propose a way to improve and apply the method for future measurements.

Hagfish genome elucidates vertebrate whole-genome duplication events and their evolutionary consequences.

Polyploidy or whole-genome duplication (WGD) is a major event that drastically reshapes genome architecture and is often assumed to be causally associated with organismal innovations and radiations. The 2R hypothesis suggests that two WGD events (1R and 2R) occurred during early vertebrate evolution. However, the timing of the 2R event relative to the divergence of gnathostomes (jawed vertebrates) and cyclostomes (jawless hagfishes and lampreys) is unresolved and whether these WGD events underlie vertebrate phenotypic diversification remains elusive. Here we present the genome of the inshore hagfish, Eptatretus burgeri. Through comparative analysis with lamprey and gnathostome genomes, we reconstruct the early events in cyclostome genome evolution, leveraging insights into the ancestral vertebrate genome. Genome-wide synteny and phylogenetic analyses support a scenario in which 1R occurred in the vertebrate stem-lineage during the early Cambrian, and 2R occurred in the gnathostome stem-lineage, maximally in the late Cambrian-earliest Ordovician, after its divergence from cyclostomes. We find that the genome of stem-cyclostomes experienced an additional independent genome triplication. Functional genomic and morphospace analyses demonstrate that WGD events generally contribute to developmental evolution with similar changes in the regulatory genome of both vertebrate groups. However, appreciable morphological diversification occurred only in the gnathostome but not in the cyclostome lineage, calling into question the general expectation that WGDs lead to leaps of bodyplan complexity.

Can resistance training improve mental health outcomes in older adults? A systematic review and meta-analysis of randomized controlled trials.

Purpose This systematic review and meta-analysis aimed to analyze the effects of resistance training (RT) and to compare the different RT prescriptions, sample characteristics, and mental health outcomes (depressive and anxiety symptoms) in older adults. Methods All studies that were available on 28th April 2023. For the analysis of intervention effects on depressive and anxiety symptoms, standardized mean differences and standard errors were calculated. Meta-analyses using random-effects models, employing robust variance meta-regression for multilevel data structures, with adjustments for small samples. Results For depressive symptoms, the mean effect was - 0.94 (95 %CI: -1.45 - -0.43, P< 0.01, I2= 93.4 %), and for anxiety symptoms, the mean effect was -1.33 (95 %CI: -2.10 - -0.56, P< 0.01, I2= 92.3 %). The mean effect was -0.51 (95 %CI: -0.67 - -0.35, P< 0.01, I2= 36.7 %) for older adults without mental disorders, and those with mental disorders the mean effect was ES= -2.15 (95 %CI: -3.01 - - 1.29, P< 0.01, I2= 91.5 %). Conclusion RT was able to improve mental health outcomes in individuals with and without mental disorders, and some RT characteristics influenced the effect of RT on mental health.

Bilateral, Simultaneous Central Serous Chorioretinopathy in Association With Oral Contraception Use.

This report describes a case of bilateral, simultaneous central serous chorioretinopathy (CSCR) in a young woman on oral contraceptive pills (OCP). A 21-year-old woman with a negative past medical history presented with sudden onset of bilateral decreased vision shortly after starting OCP. Comprehensive ocular examination revealed bilateral central serous chorioretinopathy (CSCR), confirmed on retinal optical coherence tomography (OCT) and intravenous fluorescein angiography. The patient was instructed to discontinue OCP, and three weeks later, there was complete resolution of the visual symptoms and of the bilateral serous retinal detachments, documented on OCT. [Ophthalmic Surg Lasers Imaging Retina 2024;55:96-99.].

Uncovering the magnitude of African pangolin poaching with extensive nanopore DNA genotyping of seized scales.

Trade in pangolins is illegal, and yet tons of their scales and products are seized at various ports. These large seizures are challenging to process and comprehensively genotype for upstream provenance tracing and species identification for prosecution. We implemented a scalable DNA barcoding pipeline in which rapid DNA extraction and MinION sequencing were used to genotype a substantial proportion of pangolin scales subsampled from 2 record shipments seized in Singapore in 2019 (37.5 t). We used reference sequences to match the scales to phylogeographical regions of origin. In total, we identified 2346 cytochrome b (cytb) barcodes of white-bellied (Phataginus tricuspis) (from 1091 scales), black-bellied (Phataginus tetradactyla) (227 scales), and giant (Smutsia gigantea) (1028 scales) pangolins. Haplotype diversity was higher for P. tricuspis scales (121 haplotypes, 66 novel) than that for P. tetradactyla (22 haplotypes, 15 novel) and S. gigantea (25 haplotypes, 21 novel) scales. Of the novel haplotypes, 74.2% were likely from western and west-central Africa, suggesting potential resurgence of poaching and newly exploited populations in these regions. Our results illustrate the utility of extensively subsampling large seizures and outline an efficient molecular approach for rapid genetic screening that should be accessible to most forensic laboratories and enforcement agencies.

Revelación de la magnitud de la caza furtiva del pangolín africano mediante el genotipo extenso de nanoporos de ADN de escamas incautadas Resumen Aunque el mercado de pangolines es ilegal, se incautan toneladas de sus escamas y productos derivados en varios puertos comerciales. Es un reto procesar estas magnas incautaciones y obtener el genotipo completo para usarlo en la trazabilidad logística ascendente e identificación de la especie y así imponer sanciones. Implementamos una canalización escalable del código de barras de ADN en el cual usamos la extracción rápida de ADN y la secuenciación MinION para obtener el genotipo de una proporción sustancial de las escamas de pangolín submuestreadas en dos cargamentos incautados en 2019 en Singapur (37.5 t). Usamos secuencias referenciales para emparejar las escamas con las regiones filogeográficas de origen. Identificamos en total 2,346 códigos de citocromo b (cytb) del pangolín de vientre blanco (Phataginus tricuspis) (de 1,091 escamas), de vientre negro (P. tetradactyla) (227 escamas) y del pangolín gigante (Smutsia gigantea) (1,028 escamas). La diversidad de haplotipos fue mayor en las escamas de P. tricuspis (121 haplotipos, 66 nuevos) que en las de P. tetradactyla (22 haplotipos, 15 nuevos) y S. gigantea (25 haplotipos, 21 nuevos). De los haplotipos nuevos, el 74.2% probablemente provenía del occidente y centro­occidente de África, lo que sugiere un resurgimiento potencial de la caza furtiva y poblaciones recién explotadas en estas regiones. Nuestros resultados demuestran la utilidad de submuestrear extensivamente las grandes incautaciones y esboza una estrategia molecular eficiente para un análisis genético rápido que debería ser accesible para la mayoría de los laboratorios forenses y las autoridades de aplicación.

A data-driven approach to multiple-stressor impact assessment for a marine protected area.

The coastal environment is not managed in a way that considers the impact of cumulative threats, despite being subject to threats from all realms (marine, land, and atmosphere). Relationships between threats and species are often nonlinear; thus, current (linear) approaches to estimating the impact of threats may be misleading. We developed a data-driven approach to assessing cumulative impacts on ecosystems and applied it to explore nonlinear relationships between threats and a temperate reef fish community. We used data on water quality, commercial fishing, climate change, and indicators of recreational fishing and urbanization to build a cumulative threat map of the northern region in New South Wales, Australia. We used statistical models of fish abundance to quantify associations among threats and biophysical covariates and predicted where cumulative impacts are likely to have the greatest impact on fish. We also assessed the performance of no-take zones (NTZs), to protect fish from cumulative threats across 2 marine protected area networks (marine parks). Fishing had a greater impact on fish than water quality threats (i.e., percent increase above the mean for invertivores was 337% when fishing was removed and was 11% above the mean when water quality was removed inside NTZs), and fishing outside NTZs affected fish abundances inside NTZs. Quantifying the spatial influence of multiple threats enables managers to understand the multitude of management actions required to address threats.

Una estrategia basada en datos para la evaluación de impacto de múltiples estresores en un área marina protegida Resumen Los ambientes costeros no se manejan de manera que se considere el impacto de las amenazas acumulativas, a pesar de que se enfrentan a amenazas de todos los entornos (marinas, terrestres y atmosféricas). Las relaciones entre las amenazas y las especies casi siempre son no lineales; por lo tanto, las estrategias actuales (lineales) para estimar el impacto de las amenazas pueden ser engañosas. Desarrollamos una estrategia basada en datos para evaluar el impacto acumulativo sobre los ecosistemas y la aplicamos para explorar las relaciones no lineales entre las amenazas y la comunidad de peces de arrecifes templados. Usamos datos de la calidad del agua, pesca comercial, cambio climático e indicadores de pesca recreativa y urbanización para construir un mapa acumulativo de amenazas de la región norte de Nueva Gales del Sur, Australia. Usamos modelos estadísticos de la abundancia de peces para cuantificar las asociaciones entre las amenazas y las covarianzas biofísicas y pronosticamos en dónde es probable que los impactos acumulativos sean mayores sobre los peces. También evaluamos el desempeño de las zonas de veda para así proteger a los peces de las amenazas acumulativas en dos redes de áreas marinas protegidas (parques marinos). La pesca tuvo un mayor impacto que la calidad del agua sobre los peces (es decir, el incremento del porcentaje por encima de la media de depredadores de invertebrados fue de 337% cuando se eliminó la pesca y fue de 11% por encima de la media cuando se eliminó la calidad del agua dentro de las zonas de veda) y la pesca fuera de las zonas de veda afectó la abundancia de los peces dentro de ellas. La cuantificación de la influencia espacial de las múltiples amenazas permite que los gestores entiendan la multitud de acciones de manejo que se requieren para abordar las amenazas.

A multicenter evaluation of pediatric emergency department injury visits during the COVID-19 pandemic.

BACKGROUND: Injuries, the leading cause of death in children 1-17 years old, are often preventable. Injury patterns are impacted by changes in the child's environment, shifts in supervision, and caregiver stressors. The objective of this study was to evaluate the incidence and proportion of injuries, mechanisms, and severity seen in Pediatric Emergency Departments (PEDs) during the COVID-19 pandemic. METHODS: This multicenter, cross-sectional study from January 2019 through December 2020 examined visits to 40 PEDs for children < 18 years old. Injury was defined by at least one International Classification of Disease-10th revision (ICD-10) code for bodily injury (S00-T78). The main study outcomes were total and proportion of PED injury-related visits compared to all visits in March through December 2020 and to the same months in 2019. Weekly injury visits as a percentage of total PED visits were calculated for all weeks between January 2019 and December 2020. RESULTS: The study included 741,418 PED visits for injuries pre-COVID-19 pandemic (2019) and during the COVID-19 pandemic (2020). Overall PED visits from all causes decreased 27.4% in March to December 2020 compared to the same time frame in 2019; however, the proportion of injury-related PED visits in 2020 increased by 37.7%. In 2020, injured children were younger (median age 6.31 years vs 7.31 in 2019), more commonly White (54% vs 50%, p < 0.001), non-Hispanic (72% vs 69%, p < 0.001) and had private insurance (35% vs 32%, p < 0.001). Injury hospitalizations increased 2.2% (p < 0.001) and deaths increased 0.03% (p < 0.001) in 2020 compared to 2019. Mean injury severity score increased (2.2 to 2.4, p < 0.001) between 2019 and 2020. Injuries declined for struck by/against (- 4.9%) and overexertion (- 1.2%) mechanisms. Injuries proportionally increased for pedal cycles (2.8%), cut/pierce (1.5%), motor vehicle occupant (0.9%), other transportation (0.6%), fire/burn (0.5%) and firearms (0.3%) compared to all injuries in 2020 versus 2019. CONCLUSIONS: The proportion of PED injury-related visits in March through December 2020 increased compared to the same months in 2019. Racial and payor differences were noted. Mechanisms of injury seen in the PED during 2020 changed compared to 2019, and this can inform injury prevention initiatives.

p53 deficient breast cancer cells reprogram preadipocytes toward tumor-protective immunomodulatory cells.

The TP53 gene is mutated in approximately 30% of all breast cancer cases. Adipocytes and preadipocytes, which constitute a substantial fraction of the stroma of normal mammary tissue and breast tumors, undergo transcriptional, metabolic, and phenotypic reprogramming during breast cancer development and play an important role in tumor progression. We report here that p53 loss in breast cancer cells facilitates the reprogramming of preadipocytes, inducing them to acquire a unique transcriptional and metabolic program that combines impaired adipocytic differentiation with augmented cytokine expression. This, in turn, promotes the establishment of an inflammatory tumor microenvironment, including increased abundance of Ly6C+ and Ly6G+ myeloid cells and elevated expression of the immune checkpoint ligand PD-L1. We also describe a potential gain-of-function effect of common p53 missense mutations on the inflammatory reprogramming of preadipocytes. Altogether, our study implicates p53 deregulation in breast cancer cells as a driver of tumor-supportive adipose tissue reprogramming, expanding the network of non-cell autonomous mechanisms whereby p53 dysfunction may promote cancer. Further elucidation of the interplay between p53 and adipocytes within the tumor microenvironment may suggest effective therapeutic targets for the treatment of breast cancer patients.

Detection of a novel Babesia sp. in Amblyomma javanense, an ectoparasite of Sunda pangolins.

BACKGROUND: Babesia is a protozoal, tick-borne parasite that can cause life-threatening disease in humans, wildlife and domestic animals worldwide. However, in Southeast Asia, little is known about the prevalence and diversity of Babesia species present in wildlife and the tick vectors responsible for its transmission. Recently, a novel Babesia species was reported in confiscated Sunda pangolins (Manis javanica) in Thailand. To investigate the presence of this parasite in Singapore, we conducted a molecular survey of Babesia spp. in free-roaming Sunda pangolins and their main ectoparasite, the Amblyomma javanense tick. METHODS: Ticks and tissue samples were opportunistically collected from live and dead Sunda pangolins and screened using a PCR assay targeting the 18S rRNA gene of Babesia spp. DNA barcoding of the cytochrome oxidase subunit I (COI) mitochondrial gene was used to confirm the species of ticks that were Babesia positive. RESULTS: A total of 296 ticks and 40 tissue samples were obtained from 21 Sunda pangolins throughout the 1-year study period. Babesia DNA was detected in five A. javanense ticks (minimum infection rate = 1.7%) and in nine different pangolins (52.9%) located across the country. Phylogenetic analysis revealed that the Babesia 18S sequences obtained from these samples grouped into a single monophyletic clade together with those derived from Sunda pangolins in Thailand and that this evolutionarily distinct species is basal to the Babesia sensu stricto clade, which encompasses a range of Babesia species that infect both domestic and wildlife vertebrate hosts. CONCLUSIONS: This is the first report documenting the detection of a Babesia species in A. javanense ticks, the main ectoparasite of Sunda pangolins. While our results showed that A. javanense can carry this novel Babesia sp., additional confirmatory studies are required to demonstrate vector competency. Further studies are also necessary to investigate the role of other transmission pathways given the low infection rate of ticks in relation to the high infection rate of Sunda pangolins. Although it appears that this novel Babesia sp. is of little to no pathogenicity to Sunda pangolins, its potential to cause disease in other animals or humans cannot be ruled out.

Asymmetric cortical projections to striatal direct and indirect pathways distinctly control actions.

The striatal direct and indirect pathways constitute the core for basal ganglia function in action control. Although both striatal D1- and D2-spiny projection neurons (SPNs) receive excitatory inputs from the cerebral cortex, whether or not they share inputs from the same cortical neurons, and how pathway-specific corticostriatal projections control behavior remain largely unknown. Here using a new G-deleted rabies system in mice, we found that more than two-thirds of excitatory inputs to D2-SPNs also target D1-SPNs, while only one-third do so vice versa. Optogenetic stimulation of striatal D1- vs. D2-SPN-projecting cortical neurons differently regulate locomotion, reinforcement learning and sequence behavior, implying the functional dichotomy of pathway-specific corticostriatal subcircuits. These results reveal the partially segregated yet asymmetrically overlapping cortical projections on striatal D1- vs. D2-SPNs, and that the pathway-specific corticostriatal subcircuits distinctly control behavior. It has important implications in a wide range of neurological and psychiatric diseases affecting cortico-basal ganglia circuitry.