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Asian mystery snails (Cipangopaludina chinensis Gray, 1834 and Cipangopaludina Japonica von Martens, 1861) were introduced to the United States in the 1890s and have since spread to waterbodies across the country. Besides the classic effects of invasive species, mystery snails may accumulate and distribute metals in invaded ecosystems. Few studies have evaluated this phenomenon in non-native mystery snail populations, specifically regarding partitioning of metals between different tissues and shells, and metal maternal transfer. Our goal was to compare metal concentrations (Cd, Cu, Ni, Pb, Zn) of shells, tissues, and environment of mystery snails, and the extent to which metals are maternally transferred. Mystery snails, water, and sediment were collected from several locations in northwestern Pennsylvania, USA, between 2021-2023. Metal concentrations in environmental matrices, tissues, and shells of mystery snails were evaluated via inductively coupled plasma mass spectrometry. Snail metal concentrations were compared to environmental concentrations to determine allocation between tissues and putative routes of accumulation. All five metals were detected in mystery snail tissues, with evidence of substantial accumulation of Cd, Pb, and Ni. Bioconcentration and biota sediment accumulation factors revealed that for most metals, accumulation may have occurred from water, likely reflecting snail feeding strategies and metal bioavailability. Significant correlations between maternal and offspring metal concentrations were found for all five metals, but Cu showed elevated concentrations in offspring compared to mothers. This suggests maternal transfer, increasing potential trophic transfer through predation on juvenile snails. Quantifying metal concentrations in mystery snails provides insight into potential exposure risks and trophic transfer, with implications for evaluating adverse effects in native species.

This study examined how genotypes of Daphnia pulicaria from a single population, separated by thousands of generations of evolution in the wild, differ in their sensitivity to a novel anthropogenic stressor. These genotypes were resurrected from preserved resting eggs isolated from sediments belonging to three time periods: 2002–2008, 1967–1977, and 1301–1646 A.D. Toxicity of the organophosphate insecticide chlorpyrifos was determined through a series of acute toxicity tests. There was a significant dose–response effect in all genotypes studied. Moreover, significant variation in toxicity among genotypes within each time period was detected. Importantly, a significant effect of time period on sensitivity to chlorpyrifos was found. Analysis of the median effect concentrations (EC50s) for genotypes within each time period indicated that the 1301–1646 genotypes were 2.7 times more sensitive than the 1967–1977 genotypes. This trend may be partially explained by microevolutionary shifts in response to cultural eutrophication.

Tree nurseries and greenhouses within the USDA red imported fire ant (RIFA) quarantine zone are required to incorporate insecticides into their potting media to prevent artificial spread of RIFA. Bifenthrin and fipronil are two common insecticides that are incorporated into potting media. During irrigation and stormwater events, there is potential for insecticides to leach from nursery pots, resulting in the contamination of nearby surface waters. In this study, occurrences of insecticides in simulated nursery runoff were compared with two irrigation strategies and two types of containers in single pot leaching and field runoff simulations. In addition, toxicity of pot leachate to the aquatic invertebrate, Hyallela azteca, was measured, and removal efficiencies of insecticides from bioretention cell media were evaluated. Overhead irrigation resulted in significantly higher concentrations than drip irrigation, and RootMaker® pots allowed more leaching as compared to standard slick-wall pots. However, in all tests, the average concentration of bifenthrin during 15 days of leaching in both pot and field simulations was greater than 200 ng/L; more than 100-fold greater than the LC₅₀ for H. azteca. Toxicity studies confirmed this level of toxicity. Higher amounts of compost, 20 and 40 %, in bioretention cell media resulted in greater percent reduction of both bifenthrin and fipronil. This study determined that management techniques may be able to limit the amount of insecticide that leaches from pots and runs off to receiving water bodies. Specifically, the selection of appropriate pot types, irrigation strategies, or filtering runoff through bioretention cells may reduce contamination loads. Thus, further best management strategies such as the use of bioretention cells are needed in nursery and greenhouse facilities to prevent surface water runoff from transporting toxic insecticides.

Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals. Obesity is a risk factor for severe influenza infection. Here, Almond et al show that increased susceptibility is due to increased airway concentrations of the hormone leptin which dampens interferon responses and facilitates severe infection.

Investigators seeking to identify genetic prognostic markers in a clinical trial to treat acute myeloid leukemia found that minimal residual disease, detected by the presence of mutation in NPM1, provided prognostic information independent of other risk factors. Although acute myeloid leukemia (AML) is genetically less complex than many other tumors, the condition is molecularly heterogeneous. 1 – 3 Despite improved understanding of the mutational landscape, treatment decisions, particularly regarding allogeneic stem-cell transplantation, remain guided by cytogenetic analysis, a limited panel of molecular genetic markers, and morphology-based assessment of remission. 4 – 6 Currently, a predicted risk of relapse of more than 35% is widely considered to warrant stem-cell transplantation during the first remission. 5 Patients with high-risk disease undergo stem-cell transplantation if feasible, whereas those with low-risk disease usually do not. However, there is uncertainty about the role of transplantation in patients . . .

Dietary protein dilution (DPD) promotes metabolic-remodelling and -health but the precise nutritional components driving this response remain elusive. Here, by mimicking amino acid (AA) supply from a casein-based diet, we demonstrate that restriction of dietary essential AA (EAA), but not non-EAA, drives the systemic metabolic response to total AA deprivation; independent from dietary carbohydrate supply. Furthermore, systemic deprivation of threonine and tryptophan, independent of total AA supply, are both adequate and necessary to confer the systemic metabolic response to both diet, and genetic AA-transport loss, driven AA restriction. Dietary threonine restriction (DTR) retards the development of obesity-associated metabolic dysfunction. Liver-derived fibroblast growth factor 21 is required for the metabolic remodelling with DTR. Strikingly, hepatocyte-selective establishment of threonine biosynthetic capacity reverses the systemic metabolic response to DTR. Taken together, our studies of mice demonstrate that the restriction of EAA are sufficient and necessary to confer the systemic metabolic effects of DPD. Dietary protein dilution, where protein is reduced and replaced by other nutrient sources without caloric restriction, promotes metabolic health via the hepatokine Fgf21. Here, the authors show that essential amino acids threonine and tryptophan are necessary and sufficient to induce these effects.

A human genome is sequenced and assembled de novo using a pocket-sized nanopore device. We report the sequencing and assembly of a reference genome for the human GM12878 Utah/Ceph cell line using the MinION (Oxford Nanopore Technologies) nanopore sequencer. 91.2 Gb of sequence data, representing ∼30× theoretical coverage, were produced. Reference-based alignment enabled detection of large structural variants and epigenetic modifications. De novo assembly of nanopore reads alone yielded a contiguous assembly (NG50 ∼3 Mb). We developed a protocol to generate ultra-long reads (N50 > 100 kb, read lengths up to 882 kb). Incorporating an additional 5× coverage of these ultra-long reads more than doubled the assembly contiguity (NG50 ∼6.4 Mb). The final assembled genome was 2,867 million bases in size, covering 85.8% of the reference. Assembly accuracy, after incorporating complementary short-read sequencing data, exceeded 99.8%. Ultra-long reads enabled assembly and phasing of the 4-Mb major histocompatibility complex (MHC) locus in its entirety, measurement of telomere repeat length, and closure of gaps in the reference human genome assembly GRCh38.

To evaluate the literature regarding unilateral landing biomechanics and dynamic postural stability in individuals with and without chronic ankle instability (CAI). Four online databases (PubMed, ScienceDirect, Scopus, and SportDiscus) were searched from the earliest records to 31 January 2018, as well as reference sections of related journal articles, to complete the systematic search. Studies investigating the influence of CAI on unilateral landing biomechanics and dynamic postural stability were systematically reviewed and evaluated. Twenty articles met the criteria and were included in the systematic review. Individuals with CAI were found to have deficits in dynamic postural stability on the affected limb with medium to large effect sizes and altered lower extremity kinematics, most notably in the ankle and knee, with medium to large effect sizes. Additionally, greater loading rates and peak ground reaction forces, in addition to reductions in ankle muscle activity were also found in individuals with CAI during unilateral jump-landing tasks. Individuals with CAI demonstrate dynamic postural stability deficits, lower extremity kinematic alterations, and reduced neuromuscular control during unilateral jump-landings. These are likely factors that contribute recurrent lateral ankle sprain injuries during dynamic activity in individuals with CAI. •Individuals with CAI demonstrate dynamic postural stability deficts.•Altered kinematic patterns and neuromuscular control are associated with CAI.•Clinicians should aim to restore altered movement patterns during rehabilitation.•More studies are needed to understand the link between kinetics and injury.

The domestic dog is becoming an increasingly valuable model species in medical genetics, showing particular promise to advance our understanding of cancer and orthopaedic disease. Here we undertake the largest canine genome-wide association study to date, with a panel of over 4,200 dogs genotyped at 180,000 markers, to accelerate mapping efforts. For complex diseases, we identify loci significantly associated with hip dysplasia, elbow dysplasia, idiopathic epilepsy, lymphoma, mast cell tumour and granulomatous colitis; for morphological traits, we report three novel quantitative trait loci that influence body size and one that influences fur length and shedding. Using simulation studies, we show that modestly larger sample sizes and denser marker sets will be sufficient to identify most moderate- to large-effect complex disease loci. This proposed design will enable efficient mapping of canine complex diseases, most of which have human homologues, using far fewer samples than required in human studies. The domestic dog is an important model organism for our understanding of cancer and other diseases. Here the authors conduct a genome-wide association study across multiple breeds and identify novel loci significantly associated with several complex diseases and morphological traits.

Regulatory networks underlying innate immunity continually face selective pressures to adapt to new and evolving pathogens. Transposable elements (TEs) can affect immune gene expression as a source of inducible regulatory elements, but the significance of these elements in facilitating evolutionary diversification of innate immunity remains largely unexplored. Here, we investigated the mouse epigenomic response to type II interferon (IFN) signaling and discovered that elements from a subfamily of B2 SINE (B2_Mm2) contain STAT1 binding sites and function as IFN-inducible enhancers. CRISPR deletion experiments in mouse cells demonstrated that a B2_Mm2 element has been co-opted as an enhancer driving IFN-inducible expression of Dicer1 . The rodent-specific B2 SINE family is highly abundant in the mouse genome and elements have been previously characterized to exhibit promoter, insulator, and non-coding RNA activity. Our work establishes a new role for B2 elements as inducible enhancer elements that influence mouse immunity, and exemplifies how lineage-specific TEs can facilitate evolutionary turnover and divergence of innate immune regulatory networks.