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  1. Abstract Accurately forecasting mesovortex tornado potential within quasi-linear convective systems (QLCSs) remains a major challenge. One technique used to support QLCS tornado warning operations is the three ingredients method (3IM), which is based on system balance modulated by line-normal vertical wind shear. However, observational studies examining prolific mesovortex- and tornado-producing QLCSs have identified a substantial line-parallel component of the low-level environmental shear field, which is unaccounted for in the 3IM. Recent numerical studies suggest that line-parallel shear promotes the development of strong, cyclonic mesovortices, thereby increasing the overall likelihood of QLCS tornadoes. Motivated by these recent findings, this proof-of-concept study represents the first attempt to quantify the physical factors comprising the 3IM using a prototype composite forecast parameter QTor. QTor integrates near-storm environmental vertical wind shear components with leading-line geometry to generate system-relative probabilistic forecasts for mesovortex tornado potential. QTor is evaluated using three tornadic QLCS cases and one null case within the Warn-on-Forecast System (WoFS), leveraging object-based methods to identify QLCS structures and isolate their leading lines. Results indicate that QTor forecasts show promise in effectively identifying areas conducive to mesovortex tornado development, providing qualitatively accurate probabilistic forecasts of tornadic portions of the QLCSs with up to 3 h of lead time. Significance StatementSquall-line tornadoes are difficult to forecast due to their small size and transient nature, leading to lower predictability and shorter warning lead times compared to supercell tornadoes. This study introduces QTor, a new forecasting parameter designed to predict tornado potential within squall lines. Results indicate that QTor may effectively identify areas of increased tornado likelihood, predicting tornadic portions of a squall line over 3 h in advance. While still in early development, QTor shows great promise and has the potential to enhance squall-line tornado prediction in the future. 
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    Free, publicly-accessible full text available April 1, 2027
  2. Hoxgene clusters encode transcription factors that drive regional specialization during animal development: for example the Hox factor Ubx is expressed in the insect metathoracic (T3) wing appendages and differentiates them from T2 mesothoracic identities.Hoxtranscriptional regulation requires silencing activities that prevent spurious activation and regulatory crosstalks in the wrong tissues, but this has seldom been studied in insects other thanDrosophila, which shows a derivedHoxdislocation into two genomic clusters that disjoinedAntennapedia(Antp) andUltrabithorax(Ubx). Here, we investigated howUbxis restricted to the hindwing in butterflies, amidst a contiguousHoxcluster. By analysing Hi-C and ATAC-seq data in the butterflyJunonia coenia, we show that a Topologically Associated Domain (TAD) maintains a hindwing-enriched profile of chromatin opening aroundUbx. This TAD is bordered by a Boundary Element (BE) that separates it from a region of joined wing activity around theAntplocus. CRISPR mutational perturbation of this BE releases ectopicUbxexpression in forewings, inducing homeotic clones with hindwing identities. Further mutational interrogation of two non-coding RNA encoding regions and one putativecis-regulatory module within theUbxTAD cause rare homeotic transformations in both directions, indicating the presence of both activating and repressing chromatin features. We also describe a series of spontaneous forewing homeotic phenotypes obtained inHeliconiusbutterflies, and discuss their possible mutational basis. By leveraging the extensive wing specialization found in butterflies, our initial exploration ofUbxregulation demonstrates the existence of silencing and insulating sequences that prevent its spurious expression in forewings. 
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  3. Abstract ObjectivesThe Sherpa ethnic group living at altitude in Nepal may have experienced natural selection in response to chronic hypoxia. We have previously shown that Sherpa in Kathmandu (1400 m) possess larger spleens and a greater apnea‐induced splenic contraction compared to lowland Nepalis. This may be significant for exercise capacity at altitude as the human spleen responds to stress‐induced catecholamine secretion by an immediate contraction, which results in transiently elevated hemoglobin concentration ([Hb]). MethodsTo investigate splenic contraction in response to exercise at high‐altitude (4300 m; Pb = ~450 Torr), we recruited 63 acclimatized Sherpa (29F) and 14 Nepali non‐Sherpa (7F). Spleen volume was measured before and after maximal exercise on a cycle ergometer by ultrasonography, along with [Hb] and oxygen saturation (SpO2). ResultsResting spleen volume was larger in the Sherpa compared with Nepali non‐Sherpa (237 ± 62 vs. 165 ± 34 mL,p < .001), as was the exercise‐induced splenic contraction (Δspleen volume, 91 ± 40 vs. 38 ± 32 mL,p < .001). From rest to exercise, [Hb] increased (1.2 to 1.4 g.dl−1), SpO2decreased (~9%) and calculated arterial oxygen content (CaO2) remained stable, but there were no significant differences between groups. In Sherpa, both resting spleen volume and the Δspleen volume were modest positive predictors of the change (Δ) in [Hb] and CaO2with exercise (p‐values from .026 to .037 and R2values from 0.059 to 0.067 for the predictor variable). ConclusionsLarger spleens and greater splenic contraction may be an adaptive characteristic of Nepali Sherpa to increase CaO2during exercise at altitude, but the direct link between spleen size/function and hypoxia tolerance remains unclear. 
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  4. Abstract The human spleen contracts in response to stress‐induced catecholamine secretion, resulting in a temporary rise in haemoglobin concentration ([Hb]). Recent findings highlighted enhanced splenic response to exercise at high altitude in Sherpa, possibly due to a blunted splenic response to hypoxia. To explore the potential blunted splenic contraction in Sherpas at high altitude, we examined changes in spleen volume during hyperoxic breathing, comparing acclimatized Sherpa with acclimatized individuals of lowland ancestry. Our study included 14 non‐Sherpa (7 female) residing at altitude for a mean continuous duration of 3 months and 46 Sherpa (24 female) with an average of 4 years altitude exposure. Participants underwent a hyperoxic breathing test at altitude (4300 m; barrometric pressure = ∼430 torr;  = ∼90 torr). Throughout the test, we measured spleen volume using ultrasonography and monitored oxygen saturation (). During rest, Sherpa exhibited larger spleens (226 ± 70 mL) compared to non‐Sherpa (165 ± 34 mL;P < 0.001; effect size (ES) = 0.95, 95% CI: 0.3–1.6). In response to hyperoxia, non‐Sherpa demonstrated 22 ± 12% increase in spleen size (35 ± 17 mL, 95% CI: 20.7–48.9;P < 0.001; ES = 1.8, 95% CI: 0.93–2.66), while spleen size remained unchanged in Sherpa (−2 ± 13 mL, 95% CI: −2.4 to 7.3;P = 0.640; ES = 0.18, 95% CI: −0.10 to 0.47). Our findings suggest that Sherpa and non‐Sherpas of lowland ancestry exhibit distinct variations in spleen volume during hyperoxia at high altitude, potentially indicating two distinct splenic functions. In Sherpa, this phenomenon may signify a diminished splenic response to altitude‐related hypoxia at rest, potentially contributing to enhanced splenic contractions during physical stress. Conversely, non‐Sherpa experienced a transient increase in spleen size during hyperoxia, indicating an active tonic contraction, which may influence early altitude acclimatization in lowlanders by raising [Hb]. 
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  5. High altitude native populations exhibit physiological adaptations to environmental hypoxia. It has been hypothesized that two of these populations, Andeans and Tibetans, demonstrate distinct adaptive modes with the former characterized by increased blood oxygen content, and the latter characterized by increased blood flow. To investigate this hypothesis, we recruited two groups of healthy adults (ages 18-35) with highland ancestry who were born and currently reside at high altitude. The groups were: Andean Quechuas recruited in Cerro de Pasco, Peru (AND, n = 301) and Tibetan Sherpas recruited in Pheriche, Nepal (SHP, n = 64). Participants were tested in field laboratories using identical equipment and protocols, at nearly identical altitudes (4,330m and 4,371m, respectively). We assessed a wide variety of physiological variables at rest, submaximal exercise, and maximal exercise. We found that although some phenotypes aligned with the above hypothesis, the majority did not. For example, as predicted, AND displayed significantly lower (p<0.001) ventilatory equivalents for oxygen (VE/VO2) at rest. However, this trend reversed at maximal exercise, with AND displaying significantly higher (p<0.001) VE/VO2 than SHP. Further, contrary to the above hypothesis, we found no statistically significant differences in flow-mediated dilation between the groups. These results suggest that the adaptive modes of these populations are perhaps not as distinct as previously supposed. Given that this hypothesis was formulated on the basis of data taken at rest, our data highlights the importance of assessing physiology both at rest and exercise, to gain a more complete understanding of adaptation to high altitude. 
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