In vitro NIH3T3 mouse embryonic fibroblast cell model does not predict AAV2 or AAVdj-mediated cell transformation.

One of the potential risk factors of recombinant adeno-associated virus (rAAV)-based gene therapy is insertional mutagenesis, which has been associated with the development of hepatocellular carcinoma (HCC) in rAAV-treated neonatal mice. The objective of this study was to investigate if well-established in vitro cell transformation assays (CTA) in mouse cell lines can detect AAV2 or AAVdj-mediated cell transformation. Since AAV integration at the Rian locus in neonatal mice has been implicated in AAV-mediated HCC, an rAAV vector specifically targeting the mouse Rian locus and an additional rAAV vector previously shown to cause HCC in neonatal mice were both tested for the induction of cell transformation in NIH3T3 cells.

Seasonal variability and risk evaluation of emerging organic contaminants in European river: linking in silico and in vitro approaches to prioritize hazardous EOCs.

Emerging organic contaminants (EOCs) are a growing concern for aquatic ecosystems, underscoring the need for advanced risk assessment methodologies. This study employed an integrated approach to evaluate the risks associated with 563 EOCs across 13 monitoring sites along the Sava River in Croatia. Sampling was conducted during the winter and spring months, spanning February to May.

XIS-Temperature: A daily spatiotemporal machine-learning model for air temperature in the contiguous United States.

The challenge of reconstructing air temperature for environmental applications is to accurately estimate past exposures even where monitoring is sparse. We present XGBoost-IDW Synthesis for air temperature (XIS-Temperature), a high-resolution machine-learning model for daily minimum, mean, and maximum air temperature, covering the contiguous US from 2003 through 2023. XIS uses remote sensing (land surface temperature and vegetation) along with a parsimonious set of additional predictors to make predictions at arbitrary points, allowing the estimation of address-level exposures.

Transcriptomic analysis reveals suppression of steroidogenic acute regulatory protein in gender-specific differences in Alzheimer's disease.

Alzheimer's disease (AD)-related dementia preferentially impacts two-thirds of women and one-third of men. The steroidogenic acute regulatory (StAR) protein mediates the biosynthesis of neurosteroids that sustain diverse neuronal activities. Aging, involving neurosteroidal imbalance, is the predominant risk factor for AD causing dementia.

Disruptions in cellular communication: Molecular interplay between glutamate/NMDA signalling and MAPK pathways in neurological disorders.

Neurological disorders significantly impact the central nervous system, contributing to a growing public health crisis globally. The spectrum of these disorders includes neurodevelopmental and neurodegenerative diseases. This manuscript reviews the crucial roles of cellular signalling pathways in the pathophysiology of these conditions, focusing primarily on glutaminase/glutamate/NMDA receptor signalling, alongside the mitogen-activated protein kinase (MAPK) pathways-ERK1/2, C-JNK, and P38 MAPK.

Artificial intelligence in gastrointestinal cancers: diagnostic, prognostic, and surgical strategies.

GI (Gastrointestinal) malignancies are one of the most common and lethal cancers globally. The dawn of precision medicine and developing technologies have reduced the mortality rates for GI malignancies, underscoring the main role of early detection methods for survival rate improvement. Artificial intelligence (AI) is a new technology that may improve GI cancer screening, treatment, and therapeutic efficiency for better patient care.

Neoadjuvant Intratumoral MBT(A) Immunotherapy Prevents Distant Metastases and Recurrence in Murine Models.

Neoadjuvant immunotherapy represents a pioneering approach in the preoperative treatment of cancer, offering novel avenues for tumor reduction and improved patient outcomes by modulating the immune response. This study investigated neoadjuvant immunotherapy using intratumoral administration of mannan-BAM, Toll-like receptor ligands, and antiCD40 antibody (MBTA therapy) followed by surgery in murine models of mouse tumor tissue (MTT) pheochromocytoma, B16-F10 melanoma, and 4T1 and E0771.lmb mammary carcinomas.

Programmed cell death in nasopharyngeal carcinoma: Mechanisms and therapeutic targets.

Programmed cell death is a type of autonomic and orderly cell death mode controlled by genes that maintain homeostasis and growth. Tumor is a typical manifestation of an imbalance in environmental homeostasis in the human body. Currently, several tumor treatments are designed to trigger the death of tumor cells.

Multilevel intervention for follow-up of abnormal FIT in the safety-net: IMProving Adherence to Colonoscopy through Teams and Technology (IMPACTT).

Background: Fecal immunochemical testing (FIT) is a widely used first step for colorectal cancer (CRC) screening. Abnormal FIT results require a colonoscopy for screening completion and CRC diagnosis, but the rate of timely colonoscopy is low, especially among patients in safety-net settings. Multi-level factors at the clinic- and patient-levels influence colonoscopy completion after an abnormal FIT.

The impact of talker variability and individual differences on word learning in adults.

Studies have shown that exposure to multiple talkers during learning is beneficial in a variety of spoken language tasks, such as learning speech sounds in a second language and learning novel words in a lab context. However, not all studies find the multiple talker benefit. Some studies have found that processing benefits from exposure to multiple talkers depend on factors related to the linguistic profile of the listeners and to the cognitive demands during learning (blocked versus randomized talkers).

Adaptive behaviour during epidemics: a social risk appraisal approach to modelling dynamics.

The interaction of infectious diseases and behavioural responses to them has been the subject of widespread study. However, limited attention has been given to how broader social context shapes behavioural response. In this work, we propose a novel framework which combines two well-studied dynamic processes into a 'social risk appraisal' mechanism.

Improving influenza forecast in the tropics and subtropics: a case study of Hong Kong.

Influenza forecasts could aid public health response as shown for temperate regions, but such efforts are more challenging in the tropics and subtropics due to more irregular influenza activities. Here, we built six forecast approaches for influenza in the (sub)tropics, with six model forms designed to model seasonal infection risk (i.e.

Hovering hawkmoths exploit unsteady circulation to produce aerodynamic force.

This study employs an integrated approach, combining three-dimensional flow visualization and two-dimensional flow measurement to investigate the underlying unsteady aerodynamic mechanisms of hovering hawkmoths. Using a single vortex ring model, three aerodynamic force components, such as aerodynamic force induced by unsteady circulation, vortex loop size variation and added mass, are estimated within a dimensionless time (normalized by one wing beat cycle) range of 0.418 < < 0.

Growing with dinosaurs: a review of dinosaur reproduction and ontogeny.

Since the start of the twenty-first century, there has been a notable increase in annual publications focusing on dinosaur reproduction and ontogeny with researchers using these data to address a range of macroevolutionary questions about dinosaurs. Ontogeny, which is closely tied to osteological morphological variation, impacts several key research areas, such as taxonomic diversity, population dynamics, palaeoecology, macroevolution, as well as the physiological and reproductive factors driving ecological success. While these broad studies have significantly advanced our understanding of dinosaur evolution, they have also revealed important challenges and areas needing further investigation.

Stepwise order in protein complex assembly: approaches and emerging themes.

Protein-based nanomachines drive every cellular process. An explosion of high-resolution structures of multiprotein complexes has improved our understanding of what these machines look like and how they work, but we still know relatively little about how they assemble in living cells. For example, it has only recently been appreciated that many complexes assemble co-translationally, with at least one subunit still undergoing active translation while already interacting with other subunits.

A simple inland culture system provides insights into ascidian post-embryonic developmental physiology.

Maintenance and breeding of experimental organisms are fundamental to life sciences, but both initial and running costs, and hands-on zootechnical demands can be challenging for many laboratories. Here, we first aimed to further develop a simple protocol for reliable inland culture of tunicate model species of the genus. We cultured both and in controlled experimental conditions, with a focus on dietary variables, and quantified growth and maturation parameters.

Responsiveness to cold snaps by turtle embryos depends on exposure timing and duration.

Characterizing how organisms respond to transient temperatures may further our understanding of their susceptibility to climate change. Past studies in the freshwater turtle, , have demonstrated that the timing and duration of heat waves can have major implications for the response of genes involved in gonadal development and the production of female hatchlings. Yet, no study has considered how the response of these genes to transient cold snap exposure may affect gonadal development and the production of males.

The hummingbird's adipostat: can a simple rule explain torpor frequency and duration in hummingbirds?

Because hummingbirds are small and have an expensive mode of locomotion, they have constrained energy budgets. Torpor is used to buffer against these energetic challenges, but its frequency and duration vary. We measured lipid content, metabolic rates and torpor use in two species of migrating hummingbirds, calliope () and rufous hummingbirds () at a stopover site.

Lack of thermal acclimation in multiple indices of climate vulnerability in bumblebees.

Indices of climate vulnerability are used to predict species' vulnerability to climate change based on intrinsic physiological traits, such as thermal tolerance, thermal sensitivity and thermal acclimation, but rarely is the consistency among indices evaluated simultaneously. We compared the thermal physiology of queen bumblebees between a species experiencing local declines () and a species exhibiting continent-wide increases (). We conducted a multi-week acclimation experiment under simulated climate warming to measure critical thermal maximum (CT), critical thermal minimum (CT), the thermal sensitivity of metabolic rate and water loss rate and acclimation in each of these traits.

Parallel genetic adaptation amid a background of changing effective population sizes in divergent yellow perch () populations.

Aquatic ecosystems are highly dynamic environments vulnerable to natural and anthropogenic disturbances. High-economic-value fisheries are one of many ecosystem services affected by these disturbances, and it is critical to accurately characterize the genetic diversity and effective population sizes of valuable fish stocks through time. We used genome-wide data to reconstruct the demographic histories of economically important yellow perch () populations.

Scaling up to understand disease risk: distinct roles of host functional traits in shaping infection risk of avian malaria across different scales.

Understanding the impacts of diversity on pathogen transmission is essential for public health and biological conservation. However, how the outcome and mechanisms of the diversity-disease relationship vary across biological scales in natural systems remains elusive. In addition, although the role of host functional traits has long been established in disease ecology, its integration into the diversity-disease relationship largely falls behind.

Hummingbirds use compensatory eye movements to stabilize both rotational and translational visual motion.

To maintain stable vision, behaving animals make compensatory eye movements in response to image slip, a reflex known as the optokinetic response (OKR). Although OKR has been studied in several avian species, eye movements during flight are expected to be minimal. This is because vertebrates with laterally placed eyes typically show weak OKR to nasal-to-temporal motion (NT), which simulates typical forward locomotion, compared with temporal-to-nasal motion (TN), which simulates atypical backward locomotion.

Distinct retinal ganglion cell types in strictly subterranean, naturally microphthalmic mammals.

African mole-rats (Bathyergidae, Rodentia) are subterranean rodents that live in extensive dark underground tunnel systems and rarely emerge aboveground. They can discriminate between light and dark but show no overt visually driven behaviours except for light-avoidance responses. Their eyes and central visual system are strongly reduced but not degenerated.

Cystic Breast Disease: What to Do When It's Not So Cystic.

Cystic breast masses are a common entity encountered by breast radiologists. The imaging features of benign and malignant cystic masses may overlap, causing confusion and miscategorization with the potential to produce diagnostic delay and harm. This article provides a review of key differentiating imaging features that help guide appropriate mass characterization and treatment.