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Recently it has been shown that reprogramming of adult somatic cells into a pluripotent embryonic stem cell (ESC) - like state can be achieved by the ectopic overexpression of different transcription factors from retroviral and lentiviral vectors. We have now established reprogramming of adult and cord blood derived cells by lentiviral overexpression of four factors: Oct3/4, Sox-2, Nanog and lin28. For this aim, human lung fibroblasts and human cord blood derived endothelial progenitor cells were transduced with lentiviral vectors containing the 4 plur-ipotency associated transgenes under the control of the EF1 alpha promoter. Transduced cells were transferred to inactivated murine embryonic fibroblasts as feeder cells and further cultivated under culture conditions for human embryonic stem cells. After 3-4 weeks colonies appeared that could be transferred to fresh feeders. Resulting colonies showed an ESC-like morphology and behaved like ESCs in culture. Expression of endogenous Oct3/4, Sox2, Nanog and lin28 could be shown by RT-PCR. Further characterization of the resulting iPS like cells in particular regarding their differentiation potential is ongoing.

Ips hauseri Reitter is the most important bark beetle on Picea schrenkiana in southeast Kazakhstan, but its biology, ecology, and outbreak dynamics are poorly known. We dendrochronologically reconstructed a 200-year history of disturbances in the Kazakh Tien Shan P. schrenkiana forests. Only localized, low-severity bark beetle events occurred during the reconstructed period, indicating that extensive high-severity bark beetle outbreaks have not occurred historically in the Tien Shan spruce forest, unlike bark beetle outbreaks in spruce forests in North America, Europe, and Russia. Disturbance frequency doubled after about 1965, probably due to warming climate. Results, combined with the failure of an outbreak to fully develop after blowdown events associated with hurricane-force windstorms in 2011, indicate that prolonged drought may be necessary to sustain I. hauseri outbreaks, or that year-to-year variation in the Tien Shan weather prevents outbreak development. I. hauseri is probably less aggressive than I. typographus, at least on their natural hosts within their natural ranges.

Over the last decades, climate change has triggered an increase in the frequency of sprucebark beetle (Ips typographusL.) in Central Europe. More than 50% of forests in the Czech Republic areseriously threatened by this pest, leading to high ecological and economic losses. The exponentialincrease of bark beetle infestation hinders the implementation of costly field campaigns to prevent andmitigate its effects. Remote sensing may help to overcome such limitations as it provides frequent andspatially continuous data on vegetation condition. Using Sentinel-2 images as main input, two modelshave been developed to test the ability of this data source to map bark beetle damage and severity.All models were based on a change detection approach, and required the generation of previous forestmask and dominant species maps. The first damage mapping model was developed for 2019 and2020, and it was based on bi-temporal regressions in spruce areas to estimate forest vitality and barkbeetle damage. A second model was developed for 2020 considering all forest area, but excludingclear-cuts and completely dead areas, in order to map only changes in stands dominated by alivetrees. The three products were validated with in situ data. All the maps showed high accuracies (acc>0.80). Accuracy was higher than 0.95 and F1-score was higher than 0.88 for areas with high severity,with omission errors under 0.09 in all cases. This confirmed the ability of all the models to detectbark beetle attack at the last phases. Areas with no damage or low severity showed more complexresults. The no damage category yielded greater commission errors and relative bias (CEs=0.30-0.42,relB=0.42-0.51). The similar results obtained for 2020 leaving out clear-cuts and dead trees provedthat the proposed methods could be used to help forest managers fight bark beetle pests. These bioticdamage products based on Sentinel-2 can be set up for any location to derive regular forest vitalitymaps and inform of early damage.

Heat and drought affect plant chemical defenses and thereby plant susceptibility to pests and pathogens. Monoterpenes are of particular importance for conifers as they play critical roles in defense against bark beetles. To date, work seeking to understand the impacts of heat and drought on monoterpenes has primarily focused on young potted seedlings, leaving it unclear how older age classes that are more vulnerable to bark beetles might respond to stress. Furthermore, we lack a clear picture of what carbon resources might be prioritized to support monoterpene synthesis under drought stress. To address this, we measured needle and woody tissue monoterpene concentrations and physiological variables simultaneously from mature piñon pines (Pinus edulis) from a unique temperature and drought manipulation field experiment. While heat had no effect on total monoterpene concentrations, trees under combined heat and drought stress exhibited ~ 85% and 35% increases in needle and woody tissue, respectively, over multiple years. Plant physiological variables like maximum photosynthesis each explained less than 10% of the variation in total monoterpenes for both tissue types while starch and glucose + fructose measured 1-month prior explained ~ 45% and 60% of the variation in woody tissue total monoterpene concentrations. Although total monoterpenes increased under combined stress, some key monoterpenes with known roles in bark beetle ecology decreased. These shifts may make trees more favorable for bark beetle attack rather than well defended, which one might conclude if only considering total monoterpene concentrations. Our results point to cumulative and synergistic effects of heat and drought that may reprioritize carbon allocation of specific non-structural carbohydrates toward defense.

Individual placement and support (IPS) is an evidence-based practice that helps individuals with mental illness gain and retain employment. IPS was implemented for young adults at a municipality level through a cross-sectoral collaboration between specialist mental healthcare, primary mental healthcare, and the government funded employment service (NAV). We investigated whether IPS implementation had a causal effect on employment outcomes for all young adults in receipt of a temporary health-related rehabilitation (work assessment allowance, WAA) welfare benefit, measured at the societal level compared to municipalities that did not implement IPS. We used a difference in differences design to estimate the effects of IPS implementation on the outcome of workdays per year using longitudinal registry data. We estimate the average effect of being exposed to IPS implementation during four-years of implementation compared to ten control municipalities without IPS for all WAA recipients. We found a significant, positive, causal effect on societal level employment outcomes of 5.6 ( = 0.001, 95% CI 2.7-8.4) increased workdays per year per individual, equivalent to 12.7 years of increased work in the municipality where IPS was implemented compared to municipalities without IPS. Three years after initial exposure to IPS implementation individuals worked, on average, 10.5 more days per year equating to 23.8 years of increased work. Implementing IPS as a cross sectoral collaboration at a municipality level has a significant, positive, causal, societal impact on employment outcomes for all young adults in receipt of a temporary health-related rehabilitation welfare benefit.

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold significant promise for regenerative medicine but exhibit immaturity relative to native cardiomyocytes. To make hiPSC-CMs more similar to mature cardiomyocytes, extensive research is being conducted from biochemical, electrochemical, mechanical, and physical perspectives. Quantitatively assessing their maturation is essential to evaluate improvements in cardiac cell function and clarify the impact of previous research. In this study, we present a high-speed sensing system that enables simultaneous, real-time measurement of cardiomyocyte contractile force, and intra- and extra-cellular Ca[sup.2+] dynamics. To enhance measurement precision, a visualization technique is incorporated to identify individual cardiomyocytes. This simultaneous evaluation system for cardiomyocyte contractility and various ion concentrations has the potential to become an effective and powerful foundational technology for assessing cardiomyocyte maturation and the regenerative medicine applications of IPSC-CMs. The ability to convert cardiomyocyte contractile force into single-cell force implies a more universal evaluation of the mechanical properties.

To identify accessible and permissive human cell types for efficient derivation of induced pluripotent stem cells （iPSCs）, we investigated epigenetic and gene expression signatures of multiple postnatal cell types such as fibroblasts and blood cells. Our analysis suggested that newborn cord blood （CB） and adult peripheral blood （PB） mononuclear cells （MNCs） display unique signatures that are closer to iPSCs and human embryonic stem cells （ESCs） than agematched fibroblasts to iPSCs/ESCs, thus making blood MNCs an attractive cell choice for the generation of integration-free iPSCs. Using an improved EBNA1/OriP plasmid expressing 5 reprogramming factors, we demonstrated highly efficient reprogramming of briefly cultured blood MNCs. Within 14 days of one-time transfection by one plasmid, up to 1000 iPSC-like colonies per 2 million transfected CB MNCs were generated. The efficiency of deriving iPSCs from adult PB MNCs was approximately 50-fold lower, but could be enhanced by inclusion of a second EBNA1/ OriP plasmid for transient expression of additional genes such as SV40 T antigen. The duration of obtaining bona fide iPSC colonies from adult PB MNCs was reduced to half （-14 days） as compared to adult fibroblastic cells （28- 30 days）. More than 9 human iPSC lines derived from PB or CB blood cells are extensively characterized, including those from PB MNCs of an adult patient with sickle cell disease. They lack V（D）J DNA rearrangements and vector DNA after expansion for 10-12 passages. This facile method of generating integration-free human iPSCs from blood MNCs will accelerate their use in both research and future clinical applications.

The link between mitochondria and major depressive disorder (MDD) is increasingly evident, underscored both by mitochondria’s involvement in many mechanisms identified in depression and the high prevalence of MDD in individuals with mitochondrial disorders. Mitochondrial functions and energy metabolism are increasingly considered to be involved in MDD’s pathogenesis. This study focused on cellular and mitochondrial (dys)function in two atypical cases: an antidepressant non-responding MDD patient (“Non-R”) and another with an unexplained mitochondrial disorder (“Mito”). Skin biopsies from these patients and controls were used to generate various cell types, including astrocytes and neurons, and cellular and mitochondrial functions were analyzed. Similarities were observed between the Mito patient and a broader MDD cohort, including decreased respiration and mitochondrial function. Conversely, the Non-R patient exhibited increased respiratory rates, mitochondrial calcium, and resting membrane potential. In conclusion, the Non-R patient’s data offered a new perspective on MDD, suggesting a detrimental imbalance in mitochondrial and cellular processes, rather than simply reduced functions. Meanwhile, the Mito patient’s data revealed the extensive effects of mitochondrial dysfunctions on cellular functions, potentially highlighting new MDD-associated impairments. Together, these case studies enhance our comprehension of MDD.

Both volumetric muscle loss (VML) and muscle degenerative diseases lead to an important decrease in skeletal muscle mass, condition that nowadays lacks an optimal treatment. This issue has driven towards an increasing interest in new strategies in tissue engineering, an emerging field that can offer very promising approaches. In addition, the discovery of induced pluripotent stem cells (iPSCs) has completely revolutionized the actual view of personalized medicine, and their utilization in skeletal muscle tissue engineering could, undoubtedly, add myriad benefits. In this review, we want to provide a general vision of the basic aspects to consider when engineering skeletal muscle tissue using iPSCs. Specifically, we will focus on the three main pillars of tissue engineering: the scaffold designing, the selection of the ideal cell source and the addition of factors that can enhance the resemblance with the native tissue.