Nearby and non-nested genes in the human genome have more similar genotype tissue expression.

Neighboring genes within a shared promoter arrangement (i.e. opposite direction with the neighboring ends as the transcriptional start sites) are expected to have a high similarity in genotype tissue expression due to the potential overlap in the promoter region. This raises the question of whether similarity in expression profiles depends on orientation of the neighboring genes and whether there exist thresholds of locality where the similarity diminishes. Thus, in this work, we compared genotype tissue expression profiles at different genomic orientations and localities. Interestingly, there exist gene pairs in the human genome with very high or low expression similarity. Shorter chromosomes tend to have more similarly expressed genes. Also, a cluster of 3 adjacent genes within the average range of 20 to 60 kilobase pairs can have very similar expression profiles regardless of their orientations. However, when genes are nested and in opposite orientations, a lower than expected similarity was observed. Lastly, in cases where genotype tissue expression data does not exist or have low read counts (e.g. non-coding RNA), our identified influencing range can be a first estimate of the genotype tissue expression.

The effect of visual cues at different heights on sit-to-stand movements in people with and without low back pain.

BACKGROUND: Investigating movement strategies that can be utilized to avoid pain-provocation could enhance the management of low back pain episodes. OBJECTIVE: To assess the effect of visual cues at different heights on the kinematics of sit-to-stand movements, as well as perceived difficulty and pain levels. DESIGN: Cross-over design comparing individuals with low back pain to healthy controls. METHODS: 26 asymptomatic controls and 15 individuals with chronic, recurrent low back pain performed 5 sets of 5 sit-to-stand movements. High, middle, and low visual cues were used during sets 2-4. Spinal sagittal plane range of motion, peak spinal flexion and extension angles, and trunk centre of mass velocity were obtained from kinematic data. RESULTS: The low cue led to significantly more head and lumbar spine flexion, while the high cue led to significantly more head and thoracic spine extension and increased thoracic spine range of motion. The low back pain group demonstrated a significantly lower vertical trunk centre of mass velocity than the control group during the high cue trials. There was a significant association between higher perceived difficulty scores and lower trunk centre of mass velocity for the low back pain group. Pain scores were not significantly different between cue conditions. CONCLUSION: Visual cues can be used to temporarily change the spinal kinematics of sit-to-stand movements in people with and without low back pain. This could be helpful in clinical practice to encourage more, or less, movement in specific spinal regions, and avoid pain provocation to facilitate functional rehabilitation.

Muscle short-range stiffness behaves like a maxwell element, not a spring: Implications for joint stability.

INTRODUCTION: Muscles play a critical role in supporting joints during activities of daily living, owing, in part, to the phenomenon of short-range stiffness. Briefly, when an active muscle is lengthened, bound cross-bridges are stretched, yielding forces greater than what is predicted from the force length relationship. For this reason, short-range stiffness has been proposed as an attractive mechanism for providing joint stability. However, there has yet to be a forward dynamic simulation employing a cross-bridge model, that demonstrates this stabilizing role. Therefore, the purpose of this investigation was to test whether Huxley-type muscle elements, which exhibit short-range stiffness, can stabilize a joint while at constant activation. METHODS: We analyzed the stability of an inverted pendulum (moment of inertia: 2.7 kg m2) supported by Huxley-type muscle models that reproduce the short-range stiffness phenomenon. We calculated the muscle forces that would provide sufficient short-range stiffness to stabilize the system based in minimizing the potential energy. Simulations consisted of a 50 ms long, 5 Nm square-wave perturbation, with numerical simulations carried out in ArtiSynth. RESULTS: Despite the initial analysis predicting shared activity of antagonist and agonist muscles to maintain stable equilibrium, the inverted pendulum model was not stable, and did not maintain an upright posture even with fully activated muscles. DISCUSSION & CONCLUSION: Our simulations suggested that short-range stiffness cannot be solely responsible for joint stability, even for modest perturbations. We argue that short-range stiffness cannot achieve stability because its dynamics do not behave like a typical spring. Instead, an alternative conceptual model for short-range stiffness is that of a Maxwell element (spring and damper in series), which can be obtained as a first-order approximation to the Huxley model. We postulate that the damping that results from short-range stiffness slows down the mechanical response and allows the central nervous system time to react and stabilize the joint. We speculate that other mechanisms, like reflexes or residual force enhancement/depression, may also play a role in joint stability. Joint stability is due to a combination of factors, and further research is needed to fully understand this complex system.

Heterogeneous Mechanical Stress and Interstitial Fluid Flow Predictions Derived from DCE-MRI for Rat U251N Orthotopic Gliomas.

Mechanical stress and fluid flow influence glioma cell phenotype in vitro, but measuring these quantities in vivo continues to be challenging. The purpose of this study was to predict these quantities in vivo, thus providing insight into glioma physiology and potential mechanical biomarkers that may improve glioma detection, diagnosis, and treatment. Image-based finite element models of human U251N orthotopic glioma in athymic rats were developed to predict structural stress and interstitial flow in and around each animal's tumor. In addition to accounting for structural stress caused by tumor growth, our approach has the advantage of capturing fluid pressure-induced structural stress, which was informed by in vivo interstitial fluid pressure (IFP) measurements. Because gliomas and the brain are soft, elevated IFP contributed substantially to tumor structural stress, even inverting this stress from compressive to tensile in the most compliant cases. The combination of tumor growth and elevated IFP resulted in a concentration of structural stress near the tumor boundary where it has the greatest potential to influence cell proliferation and invasion. MRI-derived anatomical geometries and tissue property distributions resulted in heterogeneous interstitial fluid flow with local maxima near cerebrospinal fluid spaces, which may promote tumor invasion and hinder drug delivery. In addition, predicted structural stress and interstitial flow varied markedly between irradiated and radiation-naïve animals. Our modeling suggests that relative to tumors in stiffer tissues, gliomas experience unusual mechanical conditions with potentially important biological (e.g., proliferation and invasion) and clinical consequences (e.g., drug delivery and treatment monitoring).

Probabilistic Nested Model Selection in Pharmacokinetic Analysis of DCE-MRI Data in Animal Model of Cerebral Tumor.

Purpose: Best current practice in the analysis of dynamic contrast enhanced (DCE)-MRI is to employ a voxel-by-voxel model selection from a hierarchy of nested models. This nested model selection (NMS) assumes that the observed time-trace of contrast-agent (CA) concentration within a voxel, corresponds to a singular physiologically nested model. However, admixtures of different models may exist within a voxel's CA time-trace. This study introduces an unsupervised feature engineering technique (Kohonen-Self-Organizing-Map (K-SOM)) to estimate the voxel-wise probability of each nested model. Methods: Sixty-six immune-compromised-RNU rats were implanted with human U-251N cancer cells, and DCE-MRI data were acquired from all the rat brains. The time-trace of change in the longitudinalrelaxivity Δ R 1 for all animals' brain voxels was calculated. DCE-MRI pharmacokinetic (PK) analysis was performed using NMS to estimate three model regions: Model-1: normal vasculature without leakage, Model-2: tumor tissues with leakage without back-flux to the vasculature, Model-3: tumor vessels with leakage and back-flux. Approximately two hundred thirty thousand (229,314) normalized Δ R 1 profiles of animals' brain voxels along with their NMS results were used to build a K-SOM (topology-size: 8×8, with competitive-learning algorithm) and probability map of each model. K-fold nested-cross-validation (NCV, k=10) was used to evaluate the performance of the K-SOM probabilistic-NMS (PNMS) technique against the NMS technique. Results: The K-SOM PNMS's estimation for the leaky tumor regions were strongly similar (Dice-Similarity-Coefficient, DSC=0.774 [CI: 0.731-0.823], and 0.866 [CI: 0.828-0.912] for Models 2 and 3, respectively) to their respective NMS regions. The mean-percent-differences (MPDs, NCV, k=10) for the estimated permeability parameters by the two techniques were: -28%, +18%, and +24%, for v p , K trans , and v e , respectively. The KSOM-PNMS technique produced microvasculature parameters and NMS regions less impacted by the arterial-input-function dispersion effect. Conclusion: This study introduces an unsupervised model-averaging technique (K-SOM) to estimate the contribution of different nested-models in PK analysis and provides a faster estimate of permeability parameters.

Art Therapy for Paediatric Pain: A Scoping Review.

Pain is common in paediatric populations and is best treated with a multi-disciplinary approach. Art therapy interventions are gaining popularity in paediatrics; however, there is limited evidence on its impact on pain outcomes in children and adolescents. The objective of this scoping review is to map current research on art therapy's impact as an intervention in paediatric populations experiencing any type of pain (i.e., acute, recurrent, and chronic). Electronic searches were conducted by a medical librarian to identify studies that used art therapy interventions in paediatric populations with pain as an outcome measure. Four reviewers independently screened and selected articles for extraction using Covidence and data were extracted from articles using study objectives. There were five studies that met the inclusion criteria. Four of the five studies reported on pain intensity and all studies reported on emotional functioning. Findings suggest art therapy interventions can be helpful for reducing pain, anxiety, stress, and fear associated with treatment. Further, there is emerging evidence that art therapy can support the management of acute and procedural pain in children. Future research should examine the impacts of integrating art therapy interventions into the multidisciplinary management of paediatric pain.

Photoinitiated Single-Crystal to Single-Crystal Redox Transformations of Titanium-Oxo Clusters.

Titanium-oxo clusters can undergo photochemical reactions under UV light, resulting in the reduction of the titanium-oxo core and oxidation of surface ligands. This is an important step in photocatalytic processes in light-absorbing Ti/O-based clusters, metal-organic frameworks, and (nano)material surfaces; however, studying the direct outcome of this photochemical process is challenging due to the fragility of the immediate photoproducts. In this report, titanium-oxo clusters [TiO(OiPr)(L)]n (n = 4, L = O2PPh2, or n = 6, L = O2CCH2tBu) undergo a two-electron photoredox reaction in the single-crystal state via an irreversible single-crystal to single-crystal (SC-SC) transformation initiated by a UV laser. The process is monitored by single crystal X-ray diffraction revealing the photoreduction of the cluster with coproduction of an (oxidized) acetone ligand, which is retained in the structure as a ligand to Ti(3+). The results demonstrate that photochemistry of inorganic molecules can be studied in the single crystal phase, allowing characterization of photoproducts which are unstable in the solution phase.

BUB1 regulates non-homologous end joining pathway to mediate radioresistance in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer subtype often treated with radiotherapy (RT). Due to its intrinsic heterogeneity and lack of effective targets, it is crucial to identify novel molecular targets that would increase RT efficacy. Here we demonstrate the role of BUB1 (cell cycle Ser/Thr kinase) in TNBC radioresistance and offer a novel strategy to improve TNBC treatment. METHODS: Gene expression analysis was performed to look at genes upregulated in TNBC patient samples compared to other subtypes. Cell proliferation and clonogenic survivals assays determined the IC50 of BUB1 inhibitor (BAY1816032) and radiation enhancement ratio (rER) with pharmacologic and genomic BUB1 inhibition. Mammary fat pad xenografts experiments were performed in CB17/SCID. The mechanism through which BUB1 inhibitor sensitizes TNBC cells to radiotherapy was delineated by γ-H2AX foci assays, BLRR, Immunoblotting, qPCR, CHX chase, and cell fractionation assays. RESULTS: BUB1 is overexpressed in BC and its expression is considerably elevated in TNBC with poor survival outcomes. Pharmacological or genomic ablation of BUB1 sensitized multiple TNBC cell lines to cell killing by radiation, although breast epithelial cells showed no radiosensitization with BUB1 inhibition. Kinase function of BUB1 is mainly accountable for this radiosensitization phenotype. BUB1 ablation also led to radiosensitization in TNBC tumor xenografts with significantly increased tumor growth delay and overall survival. Mechanistically, BUB1 ablation inhibited the repair of radiation-induced DNA double strand breaks (DSBs). BUB1 ablation stabilized phospho-DNAPKcs (S2056) following RT such that half-lives could not be estimated. In contrast, RT alone caused BUB1 stabilization, but pre-treatment with BUB1 inhibitor prevented stabilization (t1/2, ~8 h). Nuclear and chromatin-enriched fractionations illustrated an increase in recruitment of phospho- and total-DNAPK, and KAP1 to chromatin indicating that BUB1 is indispensable in the activation and recruitment of non-homologous end joining (NHEJ) proteins to DSBs. Additionally, BUB1 staining of TNBC tissue microarrays demonstrated significant correlation of BUB1 protein expression with tumor grade. CONCLUSIONS: BUB1 ablation sensitizes TNBC cell lines and xenografts to RT and BUB1 mediated radiosensitization may occur through NHEJ. Together, these results highlight BUB1 as a novel molecular target for radiosensitization in women with TNBC.

A circumpolar study unveils a positive non-linear effect of temperature on arctic arthropod availability that may reduce the risk of warming-induced trophic mismatch for breeding shorebirds.

Seasonally abundant arthropods are a crucial food source for many migratory birds that breed in the Arctic. In cold environments, the growth and emergence of arthropods are particularly tied to temperature. Thus, the phenology of arthropods is anticipated to undergo a rapid change in response to a warming climate, potentially leading to a trophic mismatch between migratory insectivorous birds and their prey. Using data from 19 sites spanning a wide temperature gradient from the Subarctic to the High Arctic, we investigated the effects of temperature on the phenology and biomass of arthropods available to shorebirds during their short breeding season at high latitudes. We hypothesized that prolonged exposure to warmer summer temperatures would generate earlier peaks in arthropod biomass, as well as higher peak and seasonal biomass. Across the temperature gradient encompassed by our study sites (>10°C in average summer temperatures), we found a 3-day shift in average peak date for every increment of 80 cumulative thawing degree-days. Interestingly, we found a linear relationship between temperature and arthropod biomass only below temperature thresholds. Higher temperatures were associated with higher peak and seasonal biomass below 106 and 177 cumulative thawing degree-days, respectively, between June 5 and July 15. Beyond these thresholds, no relationship was observed between temperature and arthropod biomass. Our results suggest that prolonged exposure to elevated temperatures can positively influence prey availability for some arctic birds. This positive effect could, in part, stem from changes in arthropod assemblages and may reduce the risk of trophic mismatch.

BUB1 Inhibition Sensitizes TNBC Cell Lines to Chemotherapy and Radiotherapy.

BUB1 is overexpressed in most human solid cancers, including breast cancer. Higher BUB1 levels are associated with a poor prognosis, especially in patients with triple-negative breast cancer (TNBC). Women with TNBC often develop resistance to chemotherapy and radiotherapy, which are still the mainstay of treatment for TNBC. Our previous studies demonstrated that a BUB1 kinase inhibitor (BAY1816032) reduced tumor cell proliferation and significantly enhanced radiotherapy efficacy in TNBC. In this study, we evaluated the effectiveness of BAY1816032 with a PARP inhibitor (olaparib), platinum agent (cisplatin), and microtubule poison (paclitaxel) alone or in combination with radiotherapy using cytotoxicity and clonogenic survival assays. BUB1 inhibitors sensitized BRCA1/2 wild-type SUM159 and MDA-MB-231 cells to olaparib, cisplatin, and paclitaxel synergistically (combination index; CI < 1). BAY1816032 significantly increased the radiation sensitization of SUM159 and MDA-MB-231 by olaparib, cisplatin, or paclitaxel at non-toxic concentrations (doses well below the IC50 concentrations). Importantly, the small molecular inhibitor of BUB1 synergistically (CI < 1) sensitized the BRCA mutant TNBC cell line HCC1937 to olaparib. Furthermore, the BUB1 inhibitor significantly increased the radiation enhancement ratio (rER) in HCC1937 cells (rER 1.34) compared to either agent alone (BUB1i rER 1.19; PARPi rER 1.04). The data presented here are significant as they provide proof that inhibition of BUB1 kinase activity sensitizes TNBC cell lines to a PARP inhibitor and radiation, irrespective of BRCA1/2 mutation status. Due to the ability of the BUB1 inhibitor to sensitize TNBC to different classes of drugs (platinum, PARPi, microtubule depolarization inhibitors), this work strongly supports the role of BUB1 as a novel molecular target to improve chemoradiation efficacy in TNBC and provides a rationale for the clinical evaluation of BAY1816032 as a chemosensitizer and chemoradiosensitizer in TNBC.

Novel Small Molecule, UTS-1401, as a Radioprotector for Total-Body Irradiation.

We report on a new radioprotector, UTS-1401, a small molecule that was synthesized (by one of us, JS) and evaluated here for its radioprotective effect against total-body irradiation (TBI). Female and male NIH Swiss mice were subjected to TBI at doses of 6.5, 7.5 and 8.5 Gy either with or without a 24 h pretreatment of UTS-1401 given ip and observed for 30 days. Survival rates were significantly increased when mice were treated with UTS-1401 compared to those not treated. The radioprotective effect of UTS-1401 was drug-dose dependent for male mice exposed to 8.5 Gy TBI with 150 mg/kg of UTS-1401 as the optimal dose. The radioprotective effect of UTS-1401 on female mice exposed to 8.5 Gy TBI was observed at 50, 100, and 150 mg/kg, with no dose response relationship noted. Female mice were more radioresistant than male mice with LD50/30 values of 7.8 Gy vs. 6.8 Gy, respectively. Weight changes after UTS-1401 alone showed a significant body weight increase at 150 mg/kg. Both the ip and iv route for UTS-1401 were similarly effective for male mice exposed to 8 Gy TBI. Further analysis using an endogenous spleen colony assay demonstrated that pretreatment of UTS-1401 for up to 72h prior to TBI protected both spleen weight and hematopoietic stem cells with a treated/untreated ratio between 2.0 and 3.2 for the latter for times between 0.5 h and 72 h. A separate in vivo study showed that pretreatment of UTS-1401 protected bone marrow CFU-GM for mice exposed to TBI. In summary, UTS-1401 is a promising small-molecule radioprotective agent as demonstrated by whole animal, hematopoietic stem cell and bone marrow myeloid progenitor cell survival.

Attentional Distractions Do Not Influence Lumbar Spine Local Dynamic Stability during Repetitive Flexion-Extension Movements.

The association between low back pain and lumbar spine local dynamic stability (LDS) appears to be modulated by if and how someone catastrophizes about pain, suggesting that the cognitive perceptions of pain may influence an individual's ability to control lumbar spine motion. Previous work also demonstrates that directing cognitive resources and attentional focus can influence movement performance. Therefore, we aimed to examine whether distracting attentional focus would influence lumbar spine LDS during repetitive flexion-extension movements. Sixteen participants performed repetitive spine flexion-extension movements under two baseline conditions (pre- and post-), and while attentional focus was distracted by either an external sensory stimulus or a cognitive-motor dual-task, both targeted at the hands. Lumbar spine LDS was examined over 30 continuous movement repetitions using maximum Lyapunov exponents. In comparison to both Baseline and Post-Baseline trials, the perceived mental workload was significantly elevated during the cognitive-motor dual-task trial but not the external sensory stimulus trial. The only statistically significant effect on LDS occurred in the Post-Baseline trial, where LDS was higher than in the cognitive-motor dual-task. In combination with previous work, these findings suggest that distracting attentional focus during repetitive lumbar spine flexion-extension movements does not have a negative influence on lumbar spine LDS.

BUB1 regulates non-homologous end joining pathway to mediate radioresistance in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer subtype often treated with radiotherapy (RT). Due to its intrinsic heterogeneity and lack of effective targets, it is crucial to identify novel molecular targets that would increase RT efficacy. Here we demonstrate the role of BUB1 (cell cycle Ser/Thr kinase) in TNBC radioresistance and offer a novel strategy to improve TNBC treatment. Methods: Gene expression analysis was performed to look at genes upregulated in TNBC patient samples compared to other subtypes. Cell proliferation and clonogenic survivals assays determined the IC 50 of BUB1 inhibitor (BAY1816032) and radiation enhancement ratio (rER) with pharmacologic and genomic BUB1 inhibition. Mammary fat pad xenografts experiments were performed in CB17/SCID. The mechanism through which BUB1 inhibitor sensitizes TNBC cells to radiotherapy was delineated by γ-H2AX foci assays, BLRR, Immunoblotting, qPCR, CHX chase, and cell fractionation assays. Results: BUB1 is overexpressed in BC and its expression is considerably elevated in TNBC with poor survival outcomes. Pharmacological or genomic ablation of BUB1 sensitized multiple TNBC cell lines to cell killing by radiation, although breast epithelial cells showed no radiosensitization with BUB1 inhibition. Kinase function of BUB1 is mainly accountable for this radiosensitization phenotype. BUB1 ablation also led to radiosensitization in TNBC tumor xenografts with significantly increased tumor growth delay and overall survival. Mechanistically, BUB1 ablation inhibited the repair of radiation-induced DNA double strand breaks (DSBs). BUB1 ablation stabilized phospho-DNAPKcs (S2056) following RT such that half-lives could not be estimated. In contrast, RT alone caused BUB1 stabilization, but pre-treatment with BUB1 inhibitor prevented stabilization (t 1/2 , ∼8 h). Nuclear and chromatin-enriched fractionations illustrated an increase in recruitment of phospho- and total-DNAPK, and KAP1 to chromatin indicating that BUB1 is indispensable in the activation and recruitment of non-homologous end joining (NHEJ) proteins to DSBs. Additionally, BUB1 staining of TNBC tissue microarrays demonstrated significant correlation of BUB1 protein expression with tumor grade. Conclusions: BUB1 ablation sensitizes TNBC cell lines and xenografts to RT and BUB1 mediated radiosensitization may occur through NHEJ. Together, these results highlight BUB1 as a novel molecular target for radiosensitization in women with TNBC.

Why do avian responses to change in Arctic green-up vary?

Global climate change has altered the timing of seasonal events (i.e., phenology) for a diverse range of biota. Within and among species, however, the degree to which alterations in phenology match climate variability differ substantially. To better understand factors driving these differences, we evaluated variation in timing of nesting of eight Arctic-breeding shorebird species at 18 sites over a 23-year period. We used the Normalized Difference Vegetation Index as a proxy to determine the start of spring (SOS) growing season and quantified relationships between SOS and nest initiation dates as a measure of phenological responsiveness. Among species, we tested four life history traits (migration distance, seasonal timing of breeding, female body mass, expected female reproductive effort) as species-level predictors of responsiveness. For one species (Semipalmated Sandpiper), we also evaluated whether responsiveness varied across sites. Although no species in our study completely tracked annual variation in SOS, phenological responses were strongest for Western Sandpipers, Pectoral Sandpipers, and Red Phalaropes. Migration distance was the strongest additional predictor of responsiveness, with longer-distance migrant species generally tracking variation in SOS more closely than species that migrate shorter distances. Semipalmated Sandpipers are a widely distributed species, but adjustments in timing of nesting relative to variability in SOS did not vary across sites, suggesting that different breeding populations of this species were equally responsive to climate cues despite differing migration strategies. Our results unexpectedly show that long-distance migrants are more sensitive to local environmental conditions, which may help them to adapt to ongoing changes in climate.

BUB1 inhibition sensitizes lung cancer cell lines to radiotherapy and chemoradiotherapy.

Background: Lung cancer is a major public health concern, with high incidence and mortality. Despite advances in targeted therapy and immunotherapy, microtubule stabilizers (paclitaxel, docetaxel), DNA intercalating platinum drugs (cisplatin) and radiation therapy continue to play a critical role in the management of locally advanced and metastatic lung cancer. Novel molecular targets would provide opportunities for improving the efficacies of radiotherapy and chemotherapy. Hypothesis: We hypothesize that BUB1 (Ser/Thr kinase) is over-expressed in lung cancers and that its inhibition will sensitize lung cancers to chemoradiation. Methods: BUB1 inhibitor (BAY1816032) was combined with platinum (cisplatin), microtubule poison (paclitaxel), a PARP inhibitor (olaparib) and radiation in cell proliferation and radiation sensitization assays. Biochemical and molecular assays were used to evaluate their impact on DNA damage signaling and cell death mechanisms. Results: BUB1 expression assessed by immunostaining of lung tumor microarrays (TMAs) confirmed higher BUB1 expression in NSCLC and SCLC compared to that of normal tissues. BUB1 overexpression in lung cancer tissues correlated directly with expression of TP53 mutations in non-small cell lung cancer (NSCLC). Elevated BUB1 levels correlated with poorer overall survival in NSCLC and small cell lung cancer (SCLC) patients. A BUB1 inhibitor (BAY1816032) synergistically sensitized lung cancer cell lines to paclitaxel and olaparib. Additionally, BAY1816032 enhanced cell killing by radiation in both NSCLC and SCLC. Molecular changes following BUB1 inhibition suggest a shift towards pro-apoptotic and anti-proliferative states, indicated by altered expression of BAX, BCL2, PCNA, and Caspases 9 and 3. Conclusion: A direct correlation between BUB1 protein expression and overall survival was shown. BUB1 inhibition sensitized both NSCLC and SCLC to various chemotherapies (cisplatin, paclitaxel) and targeted therapy (PARPi). Furthermore, we present the novel finding that BUB1 inhibition sensitized both NSCLC and SCLC to radiotherapy and chemoradiation. Our results demonstrate BUB1 inhibition as a promising strategy to sensitize lung cancers to radiation and chemoradiation therapies.

Can training to dissociate trunk and pelvic motion influence thorax-pelvis coordination and lumbar spine dynamic stability?

BACKGROUND: The large number of articulating joints within the spinal column provides an abundance of options to control its movement. However, the ability of individuals to consciously manipulate these movement options is poorly understood. OBJECTIVES: To determine if short-term training can improve the ability to consciously dissociate motion between the pelvis and thorax during repetitive pelvic tilting movements. DESIGN: Cross-over design with young healthy individuals. METHOD: Seventeen participants performed trials consisting of 35 continuous lift/lowers followed by 35 continuous anterior/posterior pelvic tilts while spine kinematics were recorded. Participants then underwent a 20-min training protocol designed to improve the control of pelvic motion and in particular the dissociation of pelvic and trunk motion. Post-training, the continuous pelvic tilt and lift/lower trials were repeated. Thorax-pelvis movement coordination was analyzed via vector coding and lumbar spine local dynamic stability was analyzed via Lyapunov exponents. Participants were grouped as being either high or low skill movers based on their ability to perform the pre-training pelvic tilt movements. RESULTS: The low skill movement group demonstrated statistically significant increases in the time spent using in-phase pelvic dominant (p = 0.028) and anti-phase pelvic dominant (p = 0.043) coordination patterns during the pelvic tilt movements after the completion of the training protocol. The high skill movement group showed no differences in their movement patterns post-training. CONCLUSIONS: Short-term training, targeted to improve the ability to dissociate pelvic from thorax motion, had a beneficial effect on the group of individuals who initially lacked skill performing the pelvic tilting task.

Genetic diversity, population structure and origin of the native goats in Central Laos.

Maintaining genetic diversity and variation in livestock populations is critical for natural and artificial selection promoting genetic improvement while avoiding problems due to inbreeding. In Laos, there are concerns that there has been a decline in genetic diversity and a rise in inbreeding among native goats in their village-based smallholder system. In this study, we investigated the genetic diversity of Lao native goats in Phin, Songkhone and Sepon districts in Central Laos for the first time using Illumina's Goat SNP50 BeadChip. We also explored the genetic relationships between Lao goats with 163 global goat populations from 36 countries. Our results revealled a close genetic relationship between Lao native goats and Chinese, Mongolian and Pakistani goats, sharing ancestries with Guangfen, Jining Grey and Luoping Yellow breeds (China) and Teddi goats (Pakistan). The observed (Ho) and expected (He) heterozygosity were 0.292 and 0.303 (Laos), 0.288 and 0.288 (Sepon), 0.299 and 0.308 (Phin) and 0.289 and 0.305 (Songkhone), respectively. There was low to moderate genetic differentiation (FST: 0.011-0.043) and negligible inbreeding coefficients (FIS: -0.001 to 0.052) between goat districts. The runs of homozygosity (ROH) had an average length of 5.92-6.85 Mb, with short ROH segments (1-5 Mb length) being the most prevalent (66.34%). Longer ROH segments (20-40 and >40 Mb length categories) were less common, comprising only 4.81% and 1.01%, respectively. Lao goats exhibit moderate genetic diversity, low-inbreeding levels and adequate effective population size. Some genetic distinctions between Lao goats may be explained by geographic and cultural features.

Associations between empirically proportionate and disproportionate fears of cancer recurrence and anxiety and depression in uveal melanoma survivors: Five-year prospective study.

OBJECTIVE: Fear of cancer recurrence (FCR) may develop into elevated anxiety or depression symptoms, but few risk factors for this development are known. Objective recurrence risk estimation is possible in some cancers. Using theories of risk communication and phobias, we examined whether the proportionality of FCR to known objective recurrence risk influences the development of anxiety and depression symptoms. METHOD: Uveal melanoma (UM) patients can opt for reliable prognostic testing. Patients experience either a 'good' or 'poor' prognostic outcome, whereby 10-year mortality due to metastatic disease is, respectively, low or high. In a five-year prospective study of a consecutive sample of 589 UM survivors, we used random intercept cross lagged panel analyses to examine whether proportionality differentially influences whether FCR progresses to anxiety and depression. RESULTS: Positive cross paths predicting anxiety from FCR were stronger in the poor prognosis group than the good prognosis and not tested groups. Prognostic group differences were not evident for depression. CONCLUSIONS: FCR was more likely to progress to elevated anxiety symptoms when proportionate to the known objective recurrence risk. Objective evidence may play a prominent role in the development and structure of fear because it assumes a high epistemic weight that activates a wide range of emotional and cognitive responses. Interventions that assist survivors to tolerate FCR in the presence of higher recurrence risks may be important in reducing anxiety symptoms.

On the Precise Link between Energy and Information.

We present a modified version of the Szilard engine, demonstrating that an explicit measurement procedure is entirely unnecessary for its operation. By considering our modified engine, we are able to provide a new interpretation of Landauer's original argument for the cost of erasure. From this view, we demonstrate that a reset operation is strictly impossible in a dynamical system with only conservative forces. Then, we prove that approaching a reset yields an unavoidable instability at the reset point. Finally, we present an original proof of Landauer's principle that is completely independent from the Second Law of thermodynamics.