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  1. The Hawaiian islands are recognized as a hotspot of biodiversity, including both surface and subsurface habitats. Recent studies of Hawaiian lava tube fauna have continued to reveal new species. Here, a new species of cave dwelling talitroid amphipod in the genus Spelaeorchestia is described from lava tubes on the island of Hawai i. It is compared with the only other known cave amphipod from the Hawaiian archipelago and with a closely related cave talitroid from Japan in the genus Minamitalitrus. 
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    Free, publicly-accessible full text available December 5, 2024
  2. Abstract Background

    Single-cell RNA sequencing (scRNA-seq) technology has enabled assessment of transcriptome-wide changes at single-cell resolution. Due to the heterogeneity in environmental exposure and genetic background across subjects, subject effect contributes to the major source of variation in scRNA-seq data with multiple subjects, which severely confounds cell type specific differential expression (DE) analysis. Moreover, dropout events are prevalent in scRNA-seq data, leading to excessive number of zeroes in the data, which further aggravates the challenge in DE analysis.

    Results

    We developed iDESC to detect cell type specific DE genes between two groups of subjects in scRNA-seq data. iDESC uses a zero-inflated negative binomial mixed model to consider both subject effect and dropouts. The prevalence of dropout events (dropout rate) was demonstrated to be dependent on gene expression level, which is modeled by pooling information across genes. Subject effect is modeled as a random effect in the log-mean of the negative binomial component. We evaluated and compared the performance of iDESC with eleven existing DE analysis methods. Using simulated data, we demonstrated that iDESC had well-controlled type I error and higher power compared to the existing methods. Applications of those methods with well-controlled type I error to three real scRNA-seq datasets from the same tissue and disease showed that the results of iDESC achieved the best consistency between datasets and the best disease relevance.

    Conclusions

    iDESC was able to achieve more accurate and robust DE analysis results by separating subject effect from disease effect with consideration of dropouts to identify DE genes, suggesting the importance of considering subject effect and dropouts in the DE analysis of scRNA-seq data with multiple subjects.

     
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  3. Free, publicly-accessible full text available June 27, 2024
  4. 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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  5. Accurate reconstruction of Laurentide Ice Sheet volume changes following the Last Glacial Maximum is critical for understanding ice sheet contribution to sea-level rise, the resulting influence of meltwater on oceanic circulation, and the spatial and temporal patterns of deglaciation. Here, we provide empirical constraints on Laurentide Ice Sheet thinning during the last deglaciation by measuring in situ cosmogenic 10Be in 81 samples collected along vertical transects of nine mountains in the northeastern United States. In conjunction with 107 exposure age samples over five vertical transects from previous studies, we reconstruct ice sheet thinning history. At peripheral sites (within 200 km of the terminal moraine), we find evidence for ∼600 m of thinning between 19.5 ka and 17.5 ka, which is coincident with the slow initial margin retreat indicated by varve records. At locations >400 km north of the terminal moraine, exposure ages above and below 1200 m a.s.l. exhibit different patterns. Ages above this elevation are variable and older, while lower elevation ages are indistinguishable over 800−1000 m elevation ranges, a pattern that suggests a subglacial thermal boundary at ∼1200 m a.s.l. separating erosive, warm-based ice below and polythermal, minimally erosive ice above. Low-elevation ages from up-ice mountains are between 15 ka and 13 ka, which suggests rapid thinning of ∼1000 m coincident with Bølling-Allerød warming. These rates of rapid paleo-ice thinning are comparable to those of other vertical exposure age transects around the world and may have been faster than modern basin-wide thinning rates in Antarctica and Greenland, which suggests that the southeastern Laurentide Ice Sheet was highly sensitive to a warming climate. 
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  6. Abstract

    Engineered whole lungs may one day expand therapeutic options for patients with end-stage lung disease. However, the feasibility of ex vivo lung regeneration remains limited by the inability to recapitulate mature, functional alveolar epithelium. Here, we modulate multimodal components of the alveolar epithelial type 2 cell (AEC2) niche in decellularized lung scaffolds in order to guide AEC2 behavior for epithelial regeneration. First, endothelial cells coordinate with fibroblasts, in the presence of soluble growth and maturation factors, to promote alveolar scaffold population with surfactant-secreting AEC2s. Subsequent withdrawal of Wnt and FGF agonism synergizes with tidal-magnitude mechanical strain to induce the differentiation of AEC2s to squamous type 1 AECs (AEC1s) in cultured alveoli, in situ. These results outline a rational strategy to engineer an epithelium of AEC2s and AEC1s contained within epithelial-mesenchymal-endothelial alveolar-like units, and highlight the critical interplay amongst cellular, biochemical, and mechanical niche cues within the reconstituting alveolus.

     
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  7. Abstract

    Infrared thermography (IRT) is a non-destructive technique capable of detection and localisation of hidden subsurface defects in components of transportation infrastructure, such as concrete bridges, thereby contributing to structural health monitoring (SHM). Addressing the lack of research on subsurface defect detection in concretes by convection heat exchange, and regarding the importance of laboratory studies for proper implementation of IRT, this paper presents results from recent laboratory investigations of IRT on concrete slabs with simulated hidden defects using a convective thermal excitation mechanism. The concrete slabs in this study had simulated defects ranging 5–25 mm in depth from the surface. These studies show the effect of initial temperature, heating/cooling process, temperature range and defect depth on thermal contrast in the concrete slabs. Furthermore, this paper compares the performance of the IRT as a non-contact sensor and thermocouples attached to the surface, in the evaluation of the thermal contrast on slabs with various defect depth. The dependence of maximum thermal contrast on the initial temperature and defect depth is explored using multivariate linear regression.

     
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  8. 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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