Affordable, sustainable technology - water supply

This paper examines three examples of affordable sustainable technology from the Cotswold area of England

Whole tumor RNA-sequencing and deconvolution reveal a clinically-prognostic PTEN/PI3K-regulated glioma transcriptional signature

The concept that solid tumors are maintained by a productive interplay between neoplastic and non-neoplastic elements has gained traction with the demonstration that stromal fibroblasts and immune system cells dictate cancer development and progression. While less studied, brain tumor (glioma) biology is likewise influenced by non-neoplastic immune system cells (macrophages and microglia) which interact with neoplastic glioma cells to create a unique physiological state (glioma ecosystem) distinct from that found in the normal tissue. To explore this neoplastic ground state, we leveraged several preclinical mouse models of neurofibromatosis type 1 (NF1) optic glioma, a low-grade astrocytoma whose formation and maintenance requires productive interactions between non-neoplastic and neoplastic cells, and employed whole tumor RNA-sequencing and mathematical deconvolution strategies to characterize this low-grade glioma ecosystem as an aggregate of cellular and acellular elements. Using this approach, we demonstrate that optic gliomas generated by altering the germlin

Graph complexity analysis identifies an ETV5 tumor-specific network in human and murine low-grade glioma

Conventional differential expression analyses have been successfully employed to identify genes whose levels change across experimental conditions. One limitation of this approach is the inability to discover central regulators that control gene expression networks. In addition, while methods for identifying central nodes in a network are widely implemented, the bioinformatics validation process and the theoretical error estimates that reflect the uncertainty in each step of the analysis are rarely considered. Using the betweenness centrality measure, we identified Etv5 as a potential tissue-level regulator in murine neurofibromatosis type 1 (Nf1) low-grade brain tumors (optic gliomas). As such, the expression of Etv5 and Etv5 target genes were increased in multiple independently-generated mouse optic glioma models relative to non-neoplastic (normal healthy) optic nerves, as well as in the cognate human tumors (pilocytic astrocytoma) relative to normal human brain. Importantly, differential Etv5 and Etv5 network expression was not directly the result of Nf1 gene dysfunction in specific cell types, but rather reflects a property of the tumor as an aggregate tissue. Moreover, this differential Etv5 expression was independently validated at the RNA and protein levels. Taken together, the combined use of network analysis, differential RNA expression findings, and experimental validation highlights the potential of the computational network approach to provide new insights into tumor biology

Intersectional Discrimination and Change in Blood Pressure Control among Older Adults: The Health and Retirement Study

BACKGROUND: Associations between multiple forms of discrimination and blood pressure control in older populations remain unestablished. METHODS: Participants were 14582 non-institutionalized individuals (59% women) in the Health and Retirement Study aged at least 51 years (76% Non-Hispanic White, 15% Non-Hispanic Black, 9% Hispanic/Latino). Primary exposures included the mean frequency of discrimination in everyday life, intersectional discrimination (defined as marginalization ascribed to more than one reason), and the sum of discrimination over the lifespan. We assessed whether discrimination was associated with change in measured hypertension status (N=14582) and concurrent medication use among reported hypertensives (N=9086) over four years (2008-2014). RESULTS: There was no association between the frequency of everyday discrimination and change in measured hypertension. Lifetime discrimination was associated with higher odds of hypertension four years later among men (OR: 1.21, 95% CI: 1.08, 1.36) but not women (OR: 0.98, 95% CI: 0.86, 1.13). Only among men, everyday discrimination due at least two reasons was associated with a 1.44 (95% CI: 1.03, 2.01)-fold odds of hypertension than reporting no everyday discrimination; reporting intersectional discrimination was not associated with developing hypertension among women (OR: 0.91, 95% CI: 0.70, 1.20). All three discriminatory measures were inversely related to time-averaged antihypertensive medication use, without apparent gender differences (e.g., OR for everyday discrimination-antihypertensive use associations: 0.85, 95% CI: 0.77, 0.94)). CONCLUSIONS: Gender differences in marginalization may more acutely elevate hypertensive risk among older men than similarly aged women. Experiences of discrimination appear to decrease the likelihood of antihypertensive medication use among older adults overall

Long-Term GPS Tracking of Ocean Sunfish Mola mola Offers a New Direction in Fish Monitoring

Satellite tracking of large pelagic fish provides insights on free-ranging behaviour, distributions and population structuring. Up to now, such fish have been tracked remotely using two principal methods: direct positioning of transmitters by Argos polar-orbiting satellites, and satellite relay of tag-derived light-level data for post hoc track reconstruction. Error fields associated with positions determined by these methods range from hundreds of metres to hundreds of kilometres. However, low spatial accuracy of tracks masks important details, such as foraging patterns. Here we use a fast-acquisition global positioning system (Fastloc GPS) tag with remote data retrieval to track long-term movements, in near real time and position accuracy of <70 m, of the world's largest bony fish, the ocean sunfish Mola mola. Search-like movements occurred over at least three distinct spatial scales. At fine scales, sunfish spent longer in highly localised areas with faster, straighter excursions between them. These ‘stopovers’ during long-distance movement appear consistent with finding and exploiting food patches. This demonstrates the feasibility of GPS tagging to provide tracks of unparalleled accuracy for monitoring movements of large pelagic fish, and with nearly four times as many locations obtained by the GPS tag than by a conventional Argos transmitter. The results signal the potential of GPS-tagged pelagic fish that surface regularly to be detectors of resource ‘hotspots’ in the blue ocean and provides a new capability for understanding large pelagic fish behaviour and habitat use that is relevant to ocean management and species conservation

Reviews

A Sword between the Sexes?: C.S. Lewis and the Gender Debates. Mary Stewart Van Leeuwen. Reviewed by Joe R. Christopher. The Cambridge Companion to C.S. Lewis. Edited by Robert MacSwain and Michael Ward. Reviewed by Gregory Bassham. The Law and Harry Potter. Jeffrey E. Thomas and Franklin G. Snyder, eds. Reviewed by Douglas C. Kane. Merlin: Knowledge and Power through the Ages. Stephen Knight. Reviewed by Harley J. Sims. Tolkien\u27s The Lord of the Rings: Sources of Inspiration. Ed. by Stratford Caldecott and Thomas Honegger. Reviewed by Charles A. Huttar. One Earth, One People: The Mythopoeic Fantasy Series of Ursula K. Le Guin, Lloyd Alexander, Madeleine L\u27Engle and Orson Scott Card. By Marek Oziewicz. Reviewed by Donna R. White. War of the Fantasy Worlds: C.S. Lewis and J.R.R. Tolkien on Art and Imagination. Martha C. Sammons. Reviewed by David Bratman

The genome sequence of the chequered fruit-tree tortrix, Pandemis corylana (Fabricius, 1794)

We present a genome assembly from an individual male Pandemis corylana (the Chequered Fruit-tree Tortrix; Arthropoda; Insecta; Lepidoptera; Tortricidae). The genome sequence is 441.6 megabases in span. Most of the assembly is scaffolded into 30 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled and is 15.53 kilobases in length. Gene annotation of this assembly on Ensembl identified 19,608 protein coding genes

Neighborhood Characteristics and Elevated Blood Pressure in Older Adults

IMPORTANCE: The local environment remains an understudied contributor to elevated blood pressure among older adults. Untargeted approaches can identify neighborhood conditions interrelated with racial segregation that drive hypertension disparities. OBJECTIVE: To evaluate independent associations of sociodemographic, economic, and housing neighborhood factors with elevated blood pressure. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, the sample included Health and Retirement Study participants who had between 1 and 3 sets of biennial sphygmomanometer readings from 2006 to 2014 or 2008 to 2016. Statistical analyses were conducted from February 5 to November 30, 2021. EXPOSURES: Fifty-one standardized American Community Survey census tract variables (2005-2009). MAIN OUTCOMES AND MEASURES: Elevated sphygmomanometer readings over the study period (6-year period prevalence): a value of at least 140 mm Hg for systolic blood pressure and/or at least 90 mm Hg for diastolic blood pressure. Participants were divided 50:50 into training and test data sets. Generalized estimating equations were used to summarize multivariable associations between each neighborhood variable and the period prevalence of elevated blood pressure, adjusting for individual-level covariates. Any neighborhood factor associated (Simes-adjusted for multiple comparisons P ≤ .05) with elevated blood pressure in the training data set was rerun in the test data set to gauge model performance. Lastly, in the full cohort, race- and ethnicity-stratified associations were evaluated for each identified neighborhood factor on the likelihood of elevated blood pressure. RESULTS: Of 12 946 participants, 4565 (35%) had elevated sphygmomanometer readings (median [IQR] age, 68 [63-73] years; 2283 [50%] male; 228 [5%] Hispanic or Latino, 502 [11%] non-Hispanic Black, and 3761 [82%] non-Hispanic White). Between 2006 and 2016, a lower likelihood of elevated blood pressure was observed (relative risk for highest vs lowest tertile, 0.91; 95% CI, 0.86-0.96) among participants residing in a neighborhood with recent (post-1999) in-migration of homeowners. This association was precise among participants with non-Hispanic White and other race and ethnicity (relative risk, 0.91; 95% CI, 0.85-0.97) but not non-Hispanic Black participants (relative risk, 0.97; 95% CI, 0.85-1.11; P = .48 for interaction) or Hispanic or Latino participants (relative risk, 0.84; 95% CI, 0.65-1.09; P = .78 for interaction). CONCLUSIONS AND RELEVANCE: In this cohort study of older adults, recent relocation of homeowners to a neighborhood was robustly associated with reduced likelihood of elevated blood pressure among White participants but not their racially and ethnically marginalized counterparts. Our findings indicate that gentrification may influence later-life blood pressure control

Morphological and mechanical properties of the human patella tendon in adult males with achondroplasia

Achondroplasia is a genetic mutation of fibroblast growth factor receptor resulting in impaired growth plate development in long bones due to lower collagen turnover. Despite the characteristic shorter stature and lower strength in Achondroplasic groups, little is known of the tendon mechanical properties under loading. The aim of this study was therefore to conduct a between measure design of patella tendon (PT) mechanical properties (stress, strain, stiffness and Young's Modulus) in 10 men with Achondroplasia (22 ± 3 years) and 17 male controls (22 ± 2 years). PT mechanical properties were measured during isometric maximal voluntary contraction (iMVC) of the knee extensors using ultrasonography. The Achondroplasic group produced 54% less stress at iMVC than controls (29.4 ± 8.0 v 64.5 ± 14.0 MPa, P 0.05). Achondroplasic PT were 47% less stiff(748 ± 93 v 1418 ± 101 N·mm-1, P < 0.001, d = 6.89) and had a 51% lower Young's modulus (0.39 ± 0.09 v 0.77 ± 0.14 GPa, P < 0.001, d = 3.46) than controls at iMVC. Achondroplasic PT are indeed more compliant than controls which may contribute to lower relative force production. The causes of higher Achondroplasic PT compliance are unclear but are likely due to the collagen related genetic mutation which causes Achondroplasia