E-cadherin interacts with EGFR resulting in hyper-activation of ERK in multiple models of breast cancer.

The loss of intercellular adhesion molecule E-cadherin is a hallmark of the epithelial-mesenchymal transition (EMT), during which tumor cells transition into an invasive phenotype. Accordingly, E-cadherin has long been considered a tumor suppressor gene; however, E-cadherin expression is paradoxically correlated with breast cancer survival rates. Using novel multi-compartment organoids and multiple in vivo models, we show that E-cadherin promotes a hyper-proliferative phenotype in breast cancer cells via interaction with the transmembrane receptor EGFR. The E-cad and EGFR interaction results in activation of the MEK/ERK signaling pathway, leading to a significant increase in proliferation via activation of transcription factors, including c-Fos. Pharmacological inhibition of MEK activity in E-cadherin positive breast cancer significantly decreases both tumor growth and macro-metastasis in vivo. This work provides evidence for a novel role of E-cadherin in breast tumor progression and identifies a new target to treat hyper-proliferative E-cadherin-positive breast tumors, thus providing the foundation to utilize E-cadherin as a biomarker for specific therapeutic success.

Classifying stages in the gonotrophic cycle of mosquitoes from images using computer vision techniques.

The ability to distinguish between the abdominal conditions of adult female mosquitoes has important utility for the surveillance and control of mosquito-borne diseases. However, doing so requires entomological training and time-consuming manual effort. Here, we design computer vision techniques to determine stages in the gonotrophic cycle of female mosquitoes from images. Our dataset was collected from 139 adult female mosquitoes across three medically important species-Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus-and all four gonotrophic stages of the cycle (unfed, fully fed, semi-gravid, and gravid). From these mosquitoes and stages, a total of 1959 images were captured on a plain background via multiple smartphones. Subsequently, we trained four distinct AI model architectures (ResNet50, MobileNetV2, EfficientNet-B0, and ConvNeXtTiny), validated them using unseen data, and compared their overall classification accuracies. Additionally, we analyzed t-SNE plots to visualize the formation of decision boundaries in a lower-dimensional space. Notably, ResNet50 and EfficientNet-B0 demonstrated outstanding performance with an overall accuracy of 97.44% and 93.59%, respectively. EfficientNet-B0 demonstrated the best overall performance considering computational efficiency, model size, training speed, and t-SNE decision boundaries. We also assessed the explainability of this EfficientNet-B0 model, by implementing Grad-CAMs-a technique that highlights pixels in an image that were prioritized for classification. We observed that the highest weight was for those pixels representing the mosquito abdomen, demonstrating that our AI model has indeed learned correctly. Our work has significant practical impact. First, image datasets for gonotrophic stages of mosquitoes are not yet available. Second, our algorithms can be integrated with existing citizen science platforms that enable the public to record and upload biological observations. With such integration, our algorithms will enable the public to contribute to mosquito surveillance and gonotrophic stage identification. Finally, we are aware of work today that uses computer vision techniques for automated mosquito species identification, and our algorithms in this paper can augment these efforts by enabling the automated detection of gonotrophic stages of mosquitoes as well.

Global mosquito observations dashboard (GMOD): creating a user-friendly web interface fueled by citizen science to monitor invasive and vector mosquitoes.

BACKGROUND: Mosquitoes and the diseases they transmit pose a significant public health threat worldwide, causing more fatalities than any other animal. To effectively combat this issue, there is a need for increased public awareness and mosquito control. However, traditional surveillance programs are time-consuming, expensive, and lack scalability. Fortunately, the widespread availability of mobile devices with high-resolution cameras presents a unique opportunity for mosquito surveillance. In response to this, the Global Mosquito Observations Dashboard (GMOD) was developed as a free, public platform to improve the detection and monitoring of invasive and vector mosquitoes through citizen science participation worldwide. METHODS: GMOD is an interactive web interface that collects and displays mosquito observation and habitat data supplied by four datastreams with data generated by citizen scientists worldwide. By providing information on the locations and times of observations, the platform enables the visualization of mosquito population trends and ranges. It also serves as an educational resource, encouraging collaboration and data sharing. The data acquired and displayed on GMOD is freely available in multiple formats and can be accessed from any device with an internet connection. RESULTS: Since its launch less than a year ago, GMOD has already proven its value. It has successfully integrated and processed large volumes of real-time data (~ 300,000 observations), offering valuable and actionable insights into mosquito species prevalence, abundance, and potential distributions, as well as engaging citizens in community-based surveillance programs. CONCLUSIONS: GMOD is a cloud-based platform that provides open access to mosquito vector data obtained from citizen science programs. Its user-friendly interface and data filters make it valuable for researchers, mosquito control personnel, and other stakeholders. With its expanding data resources and the potential for machine learning integration, GMOD is poised to support public health initiatives aimed at reducing the spread of mosquito-borne diseases in a cost-effective manner, particularly in regions where traditional surveillance methods are limited. GMOD is continually evolving, with ongoing development of powerful artificial intelligence algorithms to identify mosquito species and other features from submitted data. The future of citizen science holds great promise, and GMOD stands as an exciting initiative in this field.

Three-dimensional visualization of predatory gastropod feeding teeth with synchrotron scanning.

Several families of neogastropod mollusks independently evolved the ability to drill through mineralized prey skeletons using their own mineralized feeding teeth, sometimes with shell-softening chemical agents produced by an organ in the foot. Teeth with more durable tooth shapes should extend their use and improve predator performance, but past studies have described only the cusped-side of teeth, mostly overlooking morphologies related to functional interactions between teeth. Here, we describe the three-dimensional morphology of the central drilling tooth (rachidian) from four species of the neogastropod family Muricidae using synchrotron tomographic microscopy and assemble a three-dimensional model of a multitooth series in drilling position for two of them to investigate their dynamic form. We find two new types of articulating surfaces, including a saddle joint at either end of the rachidian and a large tongue-and-groove joint in the center. The latter has a shape that maximizes contact surface area between teeth as they rotate away from each other during drilling. Articulating joints have not been described in Neogastropod radula previously, but they are consistent with an earlier hypothesis that impact forces on individual teeth during predatory drilling are dispersed by tooth-tooth interactions.

A new species of the fish louse genus Dipteropeltis Calman, 1912 (Crustacea: Branchiura) from Peru.

Dipteropeltis is a poorly described genus of fish louse endemic to South America. In a small blackwater region within Loreto, Peru, 13 adult and juvenile specimens of an unidentified species of Dipteropeltis Calman, 1912, as well as one adult specimen of D. hirundo Calman, 1912, were observed and collected. Scanning electron and light micrographs were acquired to examine and measure key features of these specimens. Morphological differences from the two known species of Dipteropeltis, D. hirundo and D. campanaformis Neethling et al., 2014, indicate that the collected specimens represent a new species. Dipteropeltis longicaudatus sp. nov. is diagnosed by elongate abdominal lobes, a chevron-shaped carapace, and uniquely shaped maxillae. One specimen represents the longest branchiuran documented to date at 31.5 mm. Additionally, we provide the first sequence data for this genus using DNA barcoding, which corroborates our designation of a new species. Videos were also captured that document behaviors including host attachment, pulsating abdominal lobes, suction disc "walking", and swimming. Findings have implications for its teleost hosts, Triportheus albus Cope, 1872 and Brycon amazonicus Spix & Agassiz, 1829, the latter being a critical species for aquaculture and commercial fisheries in Amazonia.

A Habitat Model for Disease Vector Aedes aegypti in the Tampa Bay Area, FloridA.

Within the contiguous USA, Florida is unique in having tropical and subtropical climates, a great abundance and diversity of mosquito vectors, and high rates of human travel. These factors contribute to the state being the national ground zero for exotic mosquito-borne diseases, as evidenced by local transmission of viruses spread by Aedes aegypti, including outbreaks of dengue in 2022 and Zika in 2016. Because of limited treatment options, integrated vector management is a key part of mitigating these arboviruses. Practical knowledge of when and where mosquito populations of interest exist is critical for surveillance and control efforts, and habitat predictions at various geographic scales typically rely on ecological niche modeling. However, most of these models, usually created in partnership with academic institutions, demand resources that otherwise may be too time-demanding or difficult for mosquito control programs to replicate and use effectively. Such resources may include intensive computational requirements, high spatiotemporal resolutions of data not regularly available, and/or expert knowledge of statistical analysis. Therefore, our study aims to partner with mosquito control agencies in generating operationally useful mosquito abundance models. Given the increasing threat of mosquito-borne disease transmission in Florida, our analytic approach targets recent Ae. aegypti abundance in the Tampa Bay area. We investigate explanatory variables that: 1) are publicly available, 2) require little to no preprocessing for use, and 3) are known factors associated with Ae. aegypti ecology. Out of our 4 final models, none required more than 5 out of the 36 predictors assessed (13.9%). Similar to previous literature, the strongest predictors were consistently 3- and 4-wk temperature and precipitation lags, followed closely by 1 of 2 environmental predictors: land use/land cover or normalized difference vegetation index. Surprisingly, 3 of our 4 final models included one or more socioeconomic or demographic predictors. In general, larger sample sizes of trap collections and/or citizen science observations should result in greater confidence in model predictions and validation. However, given disparities in trap collections across jurisdictions, individual county models rather than a multicounty conglomerate model would likely yield stronger model fits. Ultimately, we hope that the results of our assessment will enable more accurate and precise mosquito surveillance and control of Ae. aegypti in Florida and beyond.

Spatial evaluation of healthcare accessibility across archipelagic communities of Maluku Province, Indonesia.

The Maluku Province is an underdeveloped region in Indonesia with over 1,340 scattered islands. Due to the limited health facilities and transportation infrastructure, access to healthcare is very challenging. Here, we combined data from various sources to locate the population clusters, health facilities, roads, and ports/docks, and then utilize geographic information systems (GIS) to estimate distances from residents to health facilities. Health workforce distribution data was then integrated to elucidate overall healthcare equity among districts in the province. The average distances to puskesmas (primary health clinics) were 8.89 km (by land) and 18.43 km (by land and water) respectively, and the average distances to hospitals were 56.19 km (by land) and 73.09 km (by land and water), with large disparities within and among districts. Analysis of health workforce data shows that 65% of 207 puskesmas lack physicians, while 49% lack midwives. Ambon, Tual, and Southeast Maluku have the highest health equity, while East Ceram, Buru, and South Buru have the lowest. In general, this study demonstrates the utility of GIS and spatial analyses, which can help identify problem areas in healthcare accessibility and equity in archipelago settings, and provide recommendations to stakeholders such as public health officials and district administrators.

Citizen Science as an Approach for Responding to the Threat of Anopheles stephensi in Africa.

Even as novel technologies emerge and medicines advance, pathogen-transmitting mosquitoes pose a deadly and accelerating public health threat. Detecting and mitigating the spread of Anopheles stephensi in Africa is now critical to the fight against malaria, as this invasive mosquito poses urgent and unprecedented risks to the continent. Unlike typical African vectors of malaria, An. stephensi breeds in both natural and artificial water reservoirs, and flourishes in urban environments. With An. stephensi beginning to take hold in heavily populated settings, citizen science surveillance supported by novel artificial intelligence (AI) technologies may offer impactful opportunities to guide public health decisions and community-based interventions. Coalitions like the Global Mosquito Alert Consortium (GMAC) and our freely available digital products can be incorporated into enhanced surveillance of An. stephensi and other vector-borne public health threats. By connecting local citizen science networks with global databases that are findable, accessible, interoperable, and reusable (FAIR), we are leveraging a powerful suite of tools and infrastructure for the early detection of, and rapid response to, (re)emerging vectors and diseases.

Artificial intelligence versus natural selection: Using computer vision techniques to classify bees and bee mimics.

Many groups of stingless insects have independently evolved mimicry of bees to fool would-be predators. To investigate this mimicry, we trained artificial intelligence (AI) algorithms-specifically, computer vision-to classify citizen scientist images of bees, bumble bees, and diverse bee mimics. For detecting bees and bumble bees, our models achieved accuracies of 91.71 % and 88.86 % , respectively. As a proxy for a natural predator, our models were poorest in detecting bee mimics that exhibit both aggressive and defensive mimicry. Using the explainable AI method of class activation maps, we validated that our models learn from appropriate components within the image, which in turn provided anatomical insights. Our t-SNE plot yielded perfect within-group clustering, as well as between-group clustering that grossly replicated the phylogeny. Ultimately, the transdisciplinary approaches herein can enhance global citizen science efforts as well as investigations of mimicry and morphology of bees and other insects.

Integrating Global Citizen Science Platforms to Enable Next-Generation Surveillance of Invasive and Vector Mosquitoes.

Mosquito-borne diseases continue to ravage humankind with >700 million infections and nearly one million deaths every year. Yet only a small percentage of the >3500 mosquito species transmit diseases, necessitating both extensive surveillance and precise identification. Unfortunately, such efforts are costly, time-consuming, and require entomological expertise. As envisioned by the Global Mosquito Alert Consortium, citizen science can provide a scalable solution. However, disparate data standards across existing platforms have thus far precluded truly global integration. Here, utilizing Open Geospatial Consortium standards, we harmonized four data streams from three established mobile apps­Mosquito Alert, iNaturalist, and GLOBE Observer's Mosquito Habitat Mapper and Land Cover­to facilitate interoperability and utility for researchers, mosquito control personnel, and policymakers. We also launched coordinated media campaigns that generated unprecedented numbers and types of observations, including successfully capturing the first images of targeted invasive and vector species. Additionally, we leveraged pooled image data to develop a toolset of artificial intelligence algorithms for future deployment in taxonomic and anatomical identification. Ultimately, by harnessing the combined powers of citizen science and artificial intelligence, we establish a next-generation surveillance framework to serve as a united front to combat the ongoing threat of mosquito-borne diseases worldwide.

The developing bird pelvis passes through ancestral dinosaurian conditions.

Living birds (Aves) have bodies substantially modified from the ancestral reptilian condition. The avian pelvis in particular experienced major changes during the transition from early archosaurs to living birds1,2. This stepwise transformation is well documented by an excellent fossil record2-4; however, the ontogenetic alterations that underly it are less well understood. We used embryological imaging techniques to examine the morphogenesis of avian pelvic tissues in three dimensions, allowing direct comparison with the fossil record. Many ancestral dinosaurian features2 (for example, a forward-facing pubis, short ilium and pubic 'boot') are transiently present in the early morphogenesis of birds and arrive at their typical 'avian' form after transitioning through a prenatal developmental sequence that mirrors the phylogenetic sequence of character acquisition. We demonstrate quantitatively that avian pelvic ontogeny parallels the non-avian dinosaur-to-bird transition and provide evidence for phenotypic covariance within the pelvis that is conserved across Archosauria. The presence of ancestral states in avian embryos may stem from this conserved covariant relationship. In sum, our data provide evidence that the avian pelvis, whose early development has been little studied5-7, evolved through terminal addition-a mechanism8-10 whereby new apomorphic states are added to the end of a developmental sequence, resulting in expression8,11 of ancestral character states earlier in that sequence. The phenotypic integration we detected suggests a previously unrecognized mechanism for terminal addition and hints that retention of ancestral states in development is common during evolutionary transitions.

Virtual and augmented reality: New tools for visualizing, analyzing, and communicating complex morphology.

Virtual and augmented reality (VR/AR) are new technologies with the power to revolutionize the study of morphology. Modern imaging approaches such as computed tomography, laser scanning, and photogrammetry have opened up a new digital world, enabling researchers to share and analyze morphological data electronically and in great detail. Because this digital data exists on a computer screen, however, it can remain difficult to understand and unintuitive to interact with. VR/AR technologies bridge the analog-to-digital divide by presenting 3D data to users in a very similar way to how they would interact with actual anatomy, while also providing a more immersive experience and greater possibilities for exploration. This manuscript describes VR/AR hardware, software, and techniques, and is designed to give practicing morphologists and educators a primer on using these technologies in their research, pedagogy, and communication to a wide variety of audiences. We also include a series of case studies from the presentations and workshop given at the 2019 International Congress of Vertebrate Morphology, and suggest best practices for the use of VR/AR in comparative morphology.

Evidence corroborates identity of isolated fossil feather as a wing covert of Archaeopteryx.

The historic fossil feather from the Jurassic Solnhofen has played a pivotal but controversial role in our evolutionary understanding of dinosaurs and birds. Recently, a study confirmed the diagnostic morphology of the feather's original calamus, but nonetheless challenged the proposed identity as an Archaeopteryx covert. However, there are errors in the results and interpretations presented. Here we show that the feather is most likely an upper major primary covert, based on its long calamus (23.3% total length) and eight other anatomical attributes. Critically, this hypothesis is independently supported by evidence of similar primary coverts in multiple specimens of Archaeopteryx-including from the same fossil site and horizon as the isolated feather. We also provide additional insights, such as an updated colour reconstruction of the entire feather as matte black, with 90% probability. Given the isolated nature of the fossil feather, we can never know the anatomical and taxonomic provenance with 100% certainty. However, based on all available evidence, the most empirical and parsimonious conclusion is that this feather represents a primary covert from the ancient wing of Archaeopteryx.

Ultraviolet light illuminates the avian nature of the Berlin Archaeopteryx skeleton.

The question of whether the iconic avialan Archaeopteryx was capable of active flapping flight or only passive gliding is still unresolved. This study contributes to this debate by reporting on two key aspects of this fossil that are visible under ultraviolet (UV) light. In contrast to previous studies, we show that most of the vertebral column of the Berlin Archaeopteryx possesses intraosseous pneumaticity, and that pneumatic structures also extend beyond the anterior thoracic vertebrae in other specimens of Archaeopteryx. With a minimum Pneumaticity Index (PI) of 0.39, Archaeopteryx had a much more lightweight skeleton than has been previously reported, comprising an air sac-driven respiratory system with the potential for a bird-like, high-performance metabolism. The neural spines of the 16th to 22nd presacral vertebrae in the Berlin Archaeopteryx are bridged by interspinal ossifications, and form a rigid notarium-like structure similar to the condition seen in modern birds. This reinforced vertebral column, combined with the extensive development of air sacs, suggests that Archaeopteryx was capable of flapping its wings for cursorial and/or aerial locomotion.

Single-donor spray-dried plasma.

BACKGROUND: Dried plasma is logistically superior for hemostasis management because it can be transported and stored under nonfrozen conditions and quickly reconstituted at the point of care, enabling prehospital administration. Velico Medical has developed a spray-drying system to be integrated into routine blood center work streams for spray drying single donor plasma units. This study compared the quality of the spray-dried plasma (on-demand plasma [ODP]) with fresh frozen plasma (FFP). STUDY DESIGN AND METHODS: ODP units (n = 60) were manufactured from never frozen fresh plasma, which was pretreated with glycine-hydrochloric acid and stored at 1to 6°C. Paired aliquots were frozen and stored at -18°C or less. After 31 to 33 days, ODP samples were reconstituted with water for injection and comprehensively characterized in parallel with paired FFP. The quantities of plasma dried and rehydration fluid were predetermined, ensuring comparable total protein concentration in ODP and paired FFP. RESULTS: ODP is comparable to FFP in global coagulation function as assessed by activated partial thromboplastin time and prothrombin time and in clot formation evaluated by thrombelastography. Compared to FFP, ODP had greater than 80% levels of functional coagulation factors and related proteins and chemistry analytes except for Factor XIII (74%). Pretreatment mitigated cleavage of high-molecular-weight von Willebrand factor multimers by spray drying and resulted in 60% vWF:ristocetin cofactor activity in ODP compared to FFP. CONCLUSIONS: ODP demonstrates coagulation function comparable to that of FFP. The spray drying system can be implemented in blood centers and is capable of producing units of ODP.

Spray-dried plasma deficient in high-molecular-weight multimers of von Willebrand factor retains hemostatic properties.

BACKGROUND: Dried plasmas can overcome logistical barriers that prevent fresh frozen plasma (FFP) usage in acute resuscitation, but processing of these products can detrimentally alter the composition. Spray-dried plasma (SpDP) from single units is deficient in high-molecular-weight multimers of von Willebrand factor (vWF), a critical facilitator of platelet adhesion and thrombus formation. We hypothesized that converting high-molecular-weight multimers to smaller-molecular-weight multimers would retain vWF's capacity to mediate platelet adhesion. STUDY DESIGN AND METHODS: SpDP obtained from untreated FFP was reconstituted with glycine-hydrochloric acid (HCl) and glycine (20 mM:50 mM) or pretreated with glycine-HCl (20 mM) or glycine-glycine-HCl (20 mM:50 mM) and reconstituted with water. In vitro hemostatic potential of SpDPs versus FFP or FFP spiked with 70 mM of glycine was evaluated, leading to a more detailed in vitro study of glycine-HCl-glycine (20 mM:50 mM) pretreated SpDP. Plasmas were combined with RBCs and platelets to observe global coagulation response. RESULTS: While vWF-ristocetin cofactor activity is significantly decreased (-41.13%; p < .0001) in SpDP, a model of vWF-mediated platelet adhesion to collagen under flow showed enhanced function (+13%; p < .01). Fewer microparticles, particularly of platelet origin, were observed in SpDP versus FFP (p < .0001). Small but significant differences in thromboelastography results were observed, although SpDP and FFP were within normal ranges. CONCLUSION: Comparable coagulability was observed in FFP and SpDP. The apparent paradox between vWF-ristocetin cofactor assay and vWF-mediated platelet adhesion may be explained by the increase in smaller multimers of vWF in SpDP, producing different outcomes in these assays.

Alligator mississippiensis sternal and shoulder girdle mobility increase stride length during high walks.

Crocodilians have played a significant role in evolutionary studies of archosaurs. Given that several major shifts in forelimb function occur within Archosauria, forelimb morphologies of living crocodilians are of particular importance in assessing locomotor evolutionary scenarios. A previous X-ray investigation of walking alligators revealed substantial movement of the shoulder girdle, but as the sternal cartilages do not show up in X-ray, the source of the mobility could not be conclusively determined. Scapulocoracoid movement was interpreted to indicate independent sliding of each coracoid at the sternocoracoid joint; however, rotations of the sternum could also produce similar displacement of the scapulocoracoids. Here, we present new data employing marker-based XROMM (X-ray reconstruction of moving morphology), wherein simultaneous biplanar X-ray video and surgically implanted radio-opaque markers permit precise measurement of the vertebral axis, sternum and coracoid in walking alligators. We found that movements of the sternum and sternocoracoid joint both contribute to shoulder girdle mobility and stride length, and that the sternocoracoid contribution was less than previously estimated. On average, the joint contributions to stride length (measured with reference to a point on the distal radius, thus excluding wrist motion) are as follows: thoracic vertebral rotation 6.2±3.7%, sternal rotation 11.1±2.5%, sternocoracoid joint 10.1±5.2%, glenohumeral joint 40.1±7.8% and elbow 31.1±4.2%. To our knowledge, this is the first evidence of sternal movement relative to the vertebral column (presumably via rib joints) contributing to stride length in tetrapods.

Molecular composition and ultrastructure of Jurassic paravian feathers.

Feathers are amongst the most complex epidermal structures known, and they have a well-documented evolutionary trajectory across non-avian dinosaurs and basal birds. Moreover, melanosome-like microbodies preserved in association with fossil plumage have been used to reconstruct original colour, behaviour and physiology. However, these putative ancient melanosomes might alternatively represent microorganismal residues, a conflicting interpretation compounded by a lack of unambiguous chemical data. We therefore used sensitive molecular imaging, supported by multiple independent analytical tests, to demonstrate that the filamentous epidermal appendages in a new specimen of the Jurassic paravian Anchiornis comprise remnant eumelanosomes and fibril-like microstructures, preserved as endogenous eumelanin and authigenic calcium phosphate. These results provide novel insights into the early evolution of feathers at the sub-cellular level, and unequivocally determine that melanosomes can be preserved in fossil feathers.