The Urothelial Cell Line UROtsa Transformed by Arsenite and Cadmium Display Basal Characteristics Associated with Muscle Invasive Urothelial Cancers

Muscle invasive urothelial carcinomas are divided into various molecular subtypes with basal and luminal subtypes being the prominent ones. The basal muscle-invasive urothelial carcinomas are generally more aggressive at presentation and significantly enriched with squamous features. Our laboratory has developed an in-vitro model of urothelial cancer by transforming the immortalized cell line UROtsa with arsenite (As3+) and cadmium (Cd2+). In this study, we characterized the tumors formed by these transformed cell lines as more basal-like based on their gene expression patterns with increased expression of KRT1, KRT5, KRT6, KRT14, KRT16, KRT17 and CD44. In addition, histological examination of these tumor transplants showed squamous features enriched in basal muscle invasive urothelial carcinomas. The expression of these genes increased in the transformed cell lines as well as in the urospheres, which are putative cancer initiating cells/stem cells derived from the cell lines. There was also increased expression of these genes in the urospheres derived from the parent UROtsa cell line. Thus, our data shows that the As3+ and Cd2+-transformed cell lines and their derived tumor transplants have gene expression profiles similar to the basal subtype of muscle invasive bladder carcinomas with tumors having enriched squamous features. The increased expression of basal markers in the urospheres suggests that stem cells may be involved in the development of squamous differentiation seen in some of the muscle invasive bladder carcinomas

Intramuscular lipid concentration increased in localized regions of the lumbar muscles following 60-day bedrest

BACKGROUND CONTEXT Prolonged bedrest induces accumulation of intramuscular lipid concentration (ILC) in the lumbar musculature; however, spatial distribution of ILC has not been determined. Artificial gravity (AG) mitigates some adaptations induced by 60-day bedrest by creating a head-to-feet force while participants are in a supine position. PURPOSE To quantify the spatial distribution of accumulation of ILC in the lumbar musculature after 60-day bedrest, and whether this can be mitigated by AG exposure. STUDY DESIGN Prospective longitudinal study. PATIENT SAMPLE Twenty-four healthy individuals (8 females) participated in the study: Eight received 30 min continuous AG (cAG); Eight received 6 × 5min AG (iAG), interspersed with rests; Eight were not exposed to AG (CRTL). OUTCOME MEASURES From 3T magnetic resonance imaging (MRI), axial images were selected to assess lumbar multifidus (LM), lumbar erector spinae (LES), quadratus lumborum (QL), and psoas major (PM) muscles from L1/L2 to L5/S1 intervertebral disc levels. Chemical shift-based 2‐echo lipid/water Dixon sequence was used to measure tissue composition. Each lumbar muscle was segmented into four equal quartiles (from medial to lateral). METHODS Participants arrived at the facility for the baseline data collection before undergoing a 60-day strict 6° head-down tilt (HDT) bedrest period. MRI of the lumbopelvic region was conducted at baseline and Day-59 of bedrest. Participants performed all activities, including hygiene, in 6° HDT and were discouraged from moving excessively or unnecessarily. RESULTS At the L4/L5 and L5/S1 intervertebral disc levels, 60-day bedrest induced a greater increase in ILC in medial and lateral regions (∼+4%) of the LM than central regions (∼+2%; P<0.05). A smaller increase in ILC was induced in the lateral region of LES (∼+1%) at L1/L2 and L2/L3 than at the centro-medial region (∼+2%; P<0.05). There was no difference between CRTL and intervention groups. CONCLUSIONS Inhomogeneous spatial distribution of accumulation of ILC was found in the lumbar musculature after 60-day bedrest. These findings might reflect pathophysiological mechanisms related to muscle disuse and contribute to localized lumbar spine dysfunction. Altered spatial distribution of ILC may impair lumbar spine function after prolonged body unloading, which could increase injury risk to vulnerable soft tissues, such as the lumbar intervertebral discs. These novel results may represent a new biomarker of lumbar deconditioning for astronauts, bedridden, sedentary individuals, or those with chronic back pain. Changes are potentially modifiable but not by the AG protocols tested here

Gluteal muscle atrophy and increased intramuscular lipid concentration are not mitigated by daily artificial gravity following 60-day head-down tilt bed rest

Exposure to spaceflight and head-down tilt (HDT) bed rest leads to decreases in the mass of the gluteal muscle. Preliminary results have suggested that interventions, such as artificial gravity (AG), can partially mitigate some of the physiological adaptations induced by HDT bed rest. However, its effect on the gluteal muscles is currently unknown. This study investigated the effects of daily AG on the gluteal muscles during 60-day HDT bed rest. Twenty-four healthy individuals participated in the study: eight received 30 minutes of continuous AG; eight received 6x5 minutes of AG, interspersed with rest periods; eight belonged to a control group. T1-Weighted Dixon magnetic resonance imaging of the hip region was conducted at baseline and day 59 of HDT bed rest to establish changes in volumes and intramuscular lipid concentration (ILC). Results showed that, across groups, muscle volumes decreased by 9.2 for gluteus maximus (GMAX), 8.0 for gluteus medius (GMED), and 10.5 for gluteus minimus after 59-day HDT bed rest (all P<0.005). The ILC increased by 1.3 for GMAX and 0.5 for GMED (both P<0.05). Neither of the AG protocols mitigated deconditioning of the gluteal muscles. Whereas all gluteal muscles atrophied, the ratio of lipids to intramuscular water increased only in GMAX and GMED muscles. These changes could impair the function of the hip joint and increased the risk of falls. The deconditioning of the gluteal muscles in space may negatively impact the hip joint stability of astronauts when reexpose to terrestrial gravity

The effects of reconditioning exercises following prolonged bed rest on lumbopelvic muscle volume and accumulation of paraspinal muscle fat

Reduced muscle size and accumulation of paraspinal muscle fat content (PFC) have been reported in lumbopelvic muscles after spaceflights and head-down tilt (HDT) bed rest. While some information is available regarding reconditioning programs on muscle atrophy recovery, the effects on the accumulation of PFC are unknown. Recently, a device (the Functional Re-adaptive Exercise Device-FRED) has been developed which aims to specifically recruit lumbopelvic muscles. This study aimed to investigate the effects of a standard reconditioning (SR) program and SR program supplemented by FRED (SR+FRED) on the recovery of the lumbopelvic muscles following 60-day HDT bed rest. Twenty-four healthy participants arrived at the facility for baseline data collection (BDC) before the bed rest period. They remained in the facility for 13-days post-HDT bed rest and were randomly allocated to one of two reconditioning programs: SR or SR+FRED. Muscle volumes of the lumbar multifidus (LM), lumbar erector spinae (LES), quadratus lumborum (QL), and psoas major (PM) muscles were measured from axial T1-weighted magnetic resonance images (MRI) at all lumbar intervertebral disc levels. PFC was determined using a chemical shift-based lipid/water Dixon sequence. Each lumbopelvic muscle was segmented into four equal quartiles (from medial to lateral). MRI of the lumbopelvic region was conducted at BDC, Day-59 of bed rest (HDT59), and Day-13 after reconditioning (R13). Comparing R13 with BDC, the volumes of the LM muscle at L4/L5 and L5/S1, LES at L1/L2, and QL at L3/L4 had not recovered (all - P<0.05), and the PM muscle remained larger at L1/L2 (P=0.001). Accumulation of PFC in the LM muscle at the L4/L5 and L5/S1 levels remained higher in the centro-medial regions at R13 than BDC (all - P<0.05). There was no difference between the two reconditioning programs. A 2-week reconditioning program was insufficient to fully restore all volumes of lumbopelvic muscles and reverse the accumulation of PFC in the muscles measured to BDC values, particularly in the LM muscle at the lower lumbar levels. These findings suggest that more extended reconditioning programs or alternative exercises may be necessary to fully restore the size and properties of the lumbopelvic muscles after prolonged bed rest

Intermittent short-arm centrifugation is a partially effective countermeasure against upright balance deterioration following 60-day head-down tilt bed rest

This study investigated whether artificial gravity (AG), induced by short-radius centrifugation, mitigated deterioration in standing balance and anticipatory postural adjustments (APAs) of trunk muscles following 60-day head-down tilt bed rest. Twenty-four participants were allocated to one of three groups: control group (N=8); 30 minutes continuous AG daily (N=8); intermittent 6x5 minutes AG daily (N=8). Before and immediately after bed rest, standing balance was assessed in four conditions: eyes open and closed on both stable and foam surfaces. Measures including sway path, root-mean-square, and peak sway velocity, sway area, sway frequency power, and sway density curve were extracted from the centre of pressure displacement. APAs were assessed during rapid arm movements using intramuscular or surface electromyography electrodes of the rectus abdominis, obliquus externus and internus abdominis, transversus abdominis, erector spinae at L1, L2, L3, and L4 vertebral levels, and deep lumbar multifidus muscles. The relative latency between the EMG onset of the deltoid and each of the trunk muscles was calculated. All three groups had poorer balance performance in most of the parameters (all P<0.05) and delayed APAs of the trunk muscles following bed rest (all P<0.05). Sway path and sway velocity were deteriorated, and sway frequency power was less in those who received intermittent AG than in the control group (all P<0.05), particularly in conditions with reduced proprioceptive feedback. These data highlight the potential of intermittent AG to mitigate deterioration of some aspects of postural control induced by gravitational unloading, but no protective effects on trunk muscle responses were observed

Ancient Lowland Maya neighborhoods: Average Nearest Neighbor analysis and kernel density models, environments, and urban scale

Many humans live in large, complex political centers, composed of multi-scalar communities including neighborhoods and districts. Both today and in the past, neighborhoods form a fundamental part of cities and are defined by their spatial, architectural, and material elements. Neighborhoods existed in ancient centers of various scales, and multiple methods have been employed to identify ancient neighborhoods in archaeological contexts. However, the use of different methods for neighborhood identification within the same spatiotemporal setting results in challenges for comparisons within and between ancient societies. Here, we focus on using a single method—combining Average Nearest Neighbor (ANN) and Kernel Density (KD) analyses of household groups—to identify potential neighborhoods based on clusters of households at 23 ancient centers across the Maya Lowlands. While a one-size-fits all model does not work for neighborhood identification everywhere, the ANN/KD method provides quantifiable data on the clustering of ancient households, which can be linked to environmental zones and urban scale. We found that centers in river valleys exhibited greater household clustering compared to centers in upland and escarpment environments. Settlement patterns on flat plains were more dispersed, with little discrete spatial clustering of households. Furthermore, we categorized the ancient Maya centers into discrete urban scales, finding that larger centers had greater variation in household spacing compared to medium-sized and smaller centers. Many larger political centers possess heterogeneity in household clustering between their civic-ceremonial cores, immediate hinterlands, and far peripheries. Smaller centers exhibit greater household clustering compared to larger ones. This paper quantitatively assesses household clustering among nearly two dozen centers across the Maya Lowlands, linking environment and urban scale to settlement patterns. The findings are applicable to ancient societies and modern cities alike; understanding how humans form multi-scalar social groupings, such as neighborhoods, is fundamental to human experience and social organization

Lumbar muscle atrophy and increased relative intramuscular lipid concentration are not mitigated by daily artificial gravity after 60-day head-down tilt bed rest

Exposure to axial unloading induces adaptations in paraspinal muscles, as shown after spaceflights. This study investigated whether daily exposure to artificial gravity (AG) mitigated lumbar spine flattening and muscle atrophy associated with 60-day head-down tilt (HDT) bed rest (Earth-based space analogue). Twenty-four healthy individuals participated in the study: Eight received 30 minutes continuous AG; eight received 6x5 minutes AG, interspersed with rest periods; eight received no AG exposure (control group). Magnetic Resonance Imaging (MRI) of the lumbopelvic region was conducted at baseline (BDC) and at day 59 of HDT (HDT59). T1-weighted images were used to assess morphology of the lumbar spine (spinal length, intervertebral disc angles, disc area) and volumes of the lumbar multifidus (LM), lumbar erector spinae (LES), quadratus lumborum (QL), and psoas major (PM) muscles from L1/L2 to L5/S1 vertebral levels. A chemical shift-based 2‐point lipid/water Dixon sequence was used to evaluate muscle composition. Results showed that: spinal length and disc area increased (P<0.05); intervertebral disc angles (P<0.05) and muscle volumes of LM, LES, and QL reduced (P<0.01); and fat/water ratio for the LM and LES muscles increased (P<0.01) after HDT59 in all groups. Neither of the AG protocols mitigated the lumbar spinal deconditioning induced by HDT bed rest. The increase in lipid/water ratio in LM and LES muscles indicates an increased relative intramuscular lipid concentration. Altered muscle composition in atrophied muscles may impair lumbar spine function after body unloading, which could increase injury risk to vulnerable soft tissues. This relationship needs further investigation

Narrow lenses for capturing the complexity of fisheries: A topic analysis of fisheries science from 1990 to 2016

Despite increased fisheries science output and publication outlets, the global crisis in fisheries management is as present as ever. Since a narrow research focus may be a contributing factor to this failure, this study uncovers topics in fisheries research and their trends over time. This interdisciplinary research evaluates whether science is diversifying fisheries research topics in an attempt to capture the complexity of the fisheries system, or whether it is multiplying research on similar topics, attempting to achieve an in-depth, but possibly marginal, understanding of a few selected components of this system. By utilizing latent Dirichlet allocation as a generative probabilistic topic model, we analyse a unique dataset consisting of 46,582 full-text articles published in the last 26 years in 21 specialized scientific fisheries journals. Among the 25 topics uncovered by the model, only one (Fisheries management) refers to the human dimension of fisheries understood as socio-ecological complex adaptive systems. The most prevalent topics in our dataset directly relating to fisheries refer to Fisheries management, Stock assessment, and Fishing gear, with Fisheries management attracting the most interest. We propose directions for future research focus that most likely could contribute to providing useful advice for successful management of fisheries