ALBERT

Beschreibung: Antibody-drug conjugates (ADCs) are innovative biopharmaceutical products in which a monoclonal antibody is linked to a small molecule drug with a stable linker. Most of the ADCs developed so far are for treating cancer, but there is enormous potential for using ADCs to treat other diseases. Currently, ten ADCs have been approved by the United States Food and Drug Administration (FDA), and more than 90 ADCs are under worldwide clinical development. Monoclonal antibodies have evolved from research tools to powerful therapeutics in the past 30 years. Tremendous strides have been made in antibody discovery, protein bioengineering, formulation, and delivery devices. This manuscript provides an overview of the biology, chemistry, and biophysical properties of each component of ADC design. This review summarizes the advances and challenges in the field to date, with an emphasis on antibody conjugation, linker-payload chemistry, novel payload classes, drug-antibody ratio (DAR), and product development. The review emphasizes the lessons learned in the development of oncology antibody conjugates and look towards future innovations enabling other therapeutic indications. The review discusses resistance mechanisms to ADCs, and give an opinion on future perspectives.

Beschreibung: Hot pepper (Capsicum annum L.) is a major spice crop and is used worldwide for its nutritional value. In the field, its plant is susceptible to various fungal diseases, including fusarium wilt, caused by soil-borne fungus Fusarium oxysporum f. sp. capsici, which can survive in the soil for several years. The infected plant can be recognized by the yellowing of older leaves and downward curling of apical shoots, followed by plant wilting and ultimately the death of the plant. The resistance mechanism in plants is controlled by a single dominant gene, and conventional plant breeding techniques are used to develop a wilt-resistant germplasm. Non-conventional techniques such as gene pyramiding and expression enhancement of antifungal genes could be used to shorten the time to develop resistance against fusarium wilt in hot peppers. In this review, we discuss different aspects of the disease and the molecular basis of resistance in chili/hot pepper plants. Furthermore, this review covers the scope of conventional and non-conventional breeding strategies and different management approaches used to tackle the disease.

Beschreibung: It is widely acknowledged that vertebrates can discriminate non-symbolic numerosity using an evolutionarily conserved system dubbed Approximate Number System (ANS). Two main approaches have been used to assess behaviourally numerosity in fish: spontaneous choice tests and operant training procedures. In the first, animals spontaneously choose between sets of biologically-relevant stimuli (e.g., conspecifics, food) differing in quantities (smaller or larger). In the second, animals are trained to associate a numerosity with a reward. Although the ability of fish to discriminate numerosity has been widely documented with these methods, the molecular bases of quantities estimation and ANS are largely unknown. Recently, we combined behavioral tasks with molecular biology assays (e.g c-fos and egr1 and other early genes expression) showing that the thalamus and the caudal region of dorso-central part of the telencephalon seem to be activated upon change in numerousness in visual stimuli. In contrast, the retina and the optic tectum mainly responded to changes in continuous magnitude such as stimulus size. We here provide a review and synthesis of these findings.

Beschreibung: A batch of pine timber sawn from butt, middle and top logs was strength graded with the visual method (classification into grading classes KW—best quality, KS—medium quality, KG—inferior quality and Reject) and with the machine strength grading method—performed with the use of a mobile timber grader (classification into C strength classes). We compared the efficiency of grading classes and strength classes, depending on the type of log from which the material was obtained (butt, middle, top). Next, a strength grading machine was used to measure the modulus of elasticity in bending (MOE) and static bending strength (MOR). The ANOVA confirmed the influence of both the log type (butt, middle, top), the C strength class, and the visual strength grading class on the values of density (DEN) and MOR. Timber density and MOR decreased from the butt log section to the top log section. The ANOVA confirmed the influence of log type on MOE values, but only to a limited extent.

Beschreibung: The objective of this study was to evaluate the effects of Bacillus subtillis PB6, chromium propionate or a combination of the two on the performance, egg and eggshell quality, nutrient metabolizability and serum biochemistry of layer breeders. White Plymouth Rock and Red Rhodes Island breeder hens at 55 weeks of age were allocated in individual cages using a completely randomized block design with 16 replicates. Hens were fed control, control + probiotic (500 g/ton of Bacillus subtilis PB6), control + CrProp (50 g/ton of chromium propionate) and control + probiotic + CrProp diets from 55 to 70 weeks of age. Productive parameters and eggshell quality as well as cortisol and blood biochemistry were grouped each 28 d as well as for the overall period. The metabolizability of nutrients and energy was determined at 70 weeks of age. In the overall period, hens fed the control + probiotic or control + probiotic + CrProp diets had significantly higher egg production, egg mass, shell percentage, thickness and shell strength. The metabolizability of dry matter, nitrogen and energy increased in hens that were fed the control + probiotic + CrProp diet. In conclusion, diets supplemented with Bacillus subtillis PB6 and chromium propionate resulted in improved productive performance, eggshell quality and nutrient metabolizability of layer breeders, without modifying serum cortisol, albumin and triglycerides.

Beschreibung: In recent years, the production and consumption of thermally modified wood (TMW) has been increasing. Offcuts and other waste generated during TMWs processing into products, as well as already disposed products based on TMWs can be an input recycled raw material for production of particleboards (PBs). In a laboratory, 16 mm thick 3-layer PBs bonded with urea-formaldehyde (UF) resin were produced at 5.8 MPa, 240 °C and 8 s pressing factor. In PBs, the particles from fresh spruce wood and mixed particles from offcuts of pine, beech, and ash TMWs were combined in weight ratios of 100:0, 80:20, 50:50 and 0:100. Thickness swelling (TS) and water absorption (WA) of PBs decreased with increased portion of TMW particles, i.e., TS after 24 h maximally about 72.3% and WA after 24 h maximally about 64%. However, mechanical properties of PBs worsened proportionally with a higher content of recycled TMW—apparently, the modulus of rupture (MOR) up to 55.5% and internal bond (IB) up to 46.2%, while negative effect of TMW particles on the modulus of elasticity (MOE) was milder. Decay resistance of PBs to the brown-rot fungus Serpula lacrymans (Schumacher ex Fries) S.F. Gray increased if they contained TMW particles, maximally about 45%, while the mould resistance of PBs containing TMW particles improved only in the first days of test. In summary, the recycled TMW particles can improve the decay and water resistance of PBs exposed to higher humidity environment. However, worsening of their mechanical properties could appear, as well.

Beschreibung: Gait and physical fitness are related to cognitive function. A decrease in motor function and physical fitness can serve as an indicator of declining global cognitive function in older adults. This study aims to use machine learning (ML) to identify important features of gait and physical fitness to predict a decline in global cognitive function in older adults. A total of three hundred and six participants aged seventy-five years or older were included in the study, and their gait performance at various speeds and physical fitness were evaluated. Eight ML models were applied to data ranked by the p-value (LP) of linear regression and the importance gain (XI) of XGboost. Five optimal features were selected using elastic net on the LP data for men, and twenty optimal features were selected using support vector machine on the XI data for women. Thus, the important features for predicting a potential decline in global cognitive function in older adults were successfully identified herein. The proposed ML approach could inspire future studies on the early detection and prevention of cognitive function decline in older adults.

Beschreibung: Poa annua is a cosmopolitan, cool-season grass species regarded as one of the most significant weeds of turfgrass. It is mainly controlled by herbicides; however, repeated use of herbicides in golf turf has resulted in the evolution of multiple-herbicide resistant P. annua. Four field experiments were performed in autumn and spring in golf turf to identify effective herbicide options to control multiple herbicide-resistant P. annua. In herbicide resistance screening, the trial site population (SA1) was found to be susceptible to amicarbazone and terbuthylazine, but resistant to simazine and metribuzin at the field rate of each herbicide. Consistent with the results of the pot study, the PSII-inhibiting herbicides amicarbazone and terbuthylazine provided the best control (80–100%) of P. annua in both autumn and spring trials with minimal damage to the turf. In contrast, the other two PSII-inhibiting herbicides, metribuzin and simazine, were relatively ineffective in controlling P. annua in the field. Indaziflam also performed well in both autumn trials and reduced P. annua occurrence by 〉75%. Pyroxasulfone and s-metolachlor only provided moderate weed control in both the autumn and spring trials, reducing P. annua occurrence by 50%. Among the nine different herbicides, amicarbazone and terbuthylazine were found to be most effective for spring and autumn application in turf. As resistance to some PSII-inhibiting herbicides has already evolved in this field population, the use of amicarbazone and terbuthylazine needs to be integrated with other herbicide modes of action and non-chemical tactics to delay the onset of resistance to them.

Beschreibung: In the first quarter of 2020, Italy became one of the earliest hotspots of COVID-19 infection, and the government imposed a lockdown. During the lockdown, an online survey of 2053 adults was conducted that asked about health behaviors and about the psychological and overall impact of COVID-19. The present study is a secondary analysis of that data. We hypothesized that self-control, higher socio-economic status, existing health conditions, and fear of infection were all inversely related to actions (or intentions) that violated the lockdown (i.e., infractions). Using partial least squares structural equation modeling (PLS-SEM), we found that only the fear of infection significantly dissuaded people from violating lockdown rules. Since it is not practical or ethical to sow a fear of infection, our study indicates that enacting rules and enforcing them firmly and fairly are important tools for containing the infection. This may become more important as vaccines become more widely available and people lose their fear of infection.

Beschreibung: Despite a keen interest in clinical research, most paramedical professionals are unwilling to play an active role. Our objective was to explore paramedical professionals’ representations of research. Using an existing database of final year paramedical students (speech therapy, occupational therapy, psychomotricity, audiometry, physiotherapy, orthoptics), we deployed a qualitative approach composed of two successive steps: (1) a free word association task, and (2) semi-structured individual interviews. Out of the 54 students who agreed to be contacted, we received 21 responses to the free word association questionnaire, and 11 interviews were conducted. The hierarchical evocation matrix revealed that the scientific representation of research is based on words defining the research and the purpose of the research. “Collaboration” was identified as being an essential part of the research process. The central core of the representation is coherent with all its components perceived as positive. The content analysis of the interviews showed a polarization around two key points: (1) participants are interested in accessing and using evidence in their practice (2) but feel less confident about and/or motivated to generate evidence themselves. This study highlights the need to develop more research-friendly environments, especially in training institutions.

Beschreibung: This study aimed to investigate the effects of multi-bacteria solid-state fermented diets with different crude fiber (CF) levels on growth performance, nutrient digestibility, and microbial flora of finishing pigs. The multi-bacteria solid-state fermented diets were made up of Lactobacillus amylovorus, Enterococcus faecalis, Bacillus subtilis, and Candida utilis. According to a 2 (factors) × 2 (levels) design, with the two factors being multi-bacteria solid-state fermentation (fed non-fermented diet or multi-bacteria fermentation) or CF levels (fed a basal diet containing 2.52% CF or 7.00% CF), a total of 36 finishing pigs (70.80 ± 5.75 kg) were divided into 4 treatments with 9 barrows per group: (1) pigs fed a diet containing 7.00% CF (HF), (2) pigs fed a multi-bacteria fermentation diet containing 7.00% CF (HFM), (3) pigs fed a diet containing 2.52% CF (LF), and (4) piglets fed a multi-bacteria fermentation diet containing 2.52% CF (LFM). This experiment lasted 28 days. The multi-bacteria solid-state fermented diet increased the backfat thickness (p 〈 0.05) and apparent total tract nutrient digestibility (ATTD) of CF, neutral detergent fiber (NDF), acid detergent fiber (ADF), crude protein (CP), 8 amino acids (Trp, Asp, Gly, Cys, Val, Met, Ile, and Leu), total essential amino acids (EAA), total non-essential amino acids (NEEA), and total amino acids (TAA) (p 〈 0.05). Multi-bacteria solid-state fermented diet increased serum concentrations of HDL-c, ABL, TP, and GLU, the serum enzyme activities of GSH-Px, T-AOC, SOD, and CAT (p 〈 0.05), the relative abundance of Lactobacillus, Oscillospira, and Coprococcus (p 〈 0.05), and the abundance of YAMINSYN3-PWY, PWY-7013, GOLPDLCAT-PWY, ARGORNPROST-PWY, and PWY-5022 pathways (p 〈 0.05). The multi-bacteria solid-state fermented diet reduced the digestion amount of CF, NDF, and ADF (p 〈 0.05), the serum concentrations of TC, TG, LDL-c, BUN, and MDA (p 〈 0.05), the relative abundance of Streptococcaceae (p 〈 0.05), and the abundance of PWY-6470, PWY0-862, HSERMETANA-PWY, LACTOSECAT-PWY, MET-SAM-PWY, PWY-6700, PWY-5347, PWY0-1061, and LACTOSECAT-PWY pathways (p 〈 0.05). The high-fiber diet increased average daily feed intake (p 〈 0.05), the serum concentrations of TC, TG, LDL-c, BUN, and MDA (p 〈 0.05), the relative abundance of Clostridiaceae_Clostridium and Coprococcus (p 〈 0.05), and the abundance of TCA-GLYOX-BYPASS, GLYCOLYSIS-TCA-GLYOX-BYPASS, and PWY-6906 pathways (p 〈 0.05). The high-fiber diet reduced chest circumference (p 〈 0.05) and ATTD of ether extract (EE), CF, NDF, ADF, Ca, CP, 18 amino acids (Trp, Thr, Val, Met, Ile, Leu, Phe, Lys, His, Arg Asp, Ser, Glu, Gly, Ala, Cys, Tyr, and Pro), EAA, NEAA, and TAA (p 〈 0.05). The high-fiber diet also reduced the serum concentrations of HDL-c, TP, ABL, and GLU, the serum enzyme activities of T-AOC, GSH-Px, SOD, and CAT (p 〈 0.05), and the relative abundance of Akkermansia and Oscillospira (p 〈 0.05). There was no significant effect of the interaction between multi-bacteria fermentation and dietary CF levels, except on the digestion amount of CF (p 〈 0.05). The 7.00% CF had a negative effect on the digestion of nutrients, but multi-bacteria solid-state fermentation diets could relieve this negative effect and increase backfat thickness. High-fiber diets and multi-bacteria solid-state fermentation improved the diversity and abundance of fecal microorganisms in finishing pigs.

Beschreibung: Sowing time, as an element, is important to improving the adaptation of cultivars to environmental conditions and to achieving high seed yields. The field experiment was conducted from 2018–2019 at the Experimental Station of Vytautas Magnus University Agriculture Academy. The experimental design included treatments with different sowing dates: eight sowing dates in 2018 and 10 sowing dates in 2019. The first sowing of spring rapeseed was carried out when the soil reached its physical maturity, i.e., it did not stick to agricultural implements and it crumbled well. The other sowing dates were every seven subsequent days. From 2018–2019, the rapeseed emerged as best in early May (3 and 4 May), and later sowing reduced the emergence of rapeseed. In 2018, most pods were formed on one plant when the rapeseed was sown (on 1 June), compared to other sowings, on average 2.8 times more. In 2019, most pods were formed by the latest-sown rapeseed (7 June), from 1.4 to 2.7 times more compared to previously sown crops. In 2018, the sowing time of spring rapeseed did not have a significant effect on the number of seeds in one pod. In 2019, it was found that the rapeseed formed most of the seeds in the pod at a similar time as in 2018: the sowings of 19 April and 7 June. The average number of seeds in the pod was significantly reduced by early sowing (5 April). In 2019, the highest 1000-seed weight was found at the earliest-sown crop (5 April), which was on average 18.0% higher compared to the later sowings. The 1000-seed weight of the last-sown rapeseed (7 June) was the lowest. In 2018, the yields of early-sown (20 April) spring rapeseed were the highest. Later sowing significantly reduced the yields by 20.7 to 48.2%. In 2019, the highest seed yield was obtained after sowing spring rapeseed in late April (26 April); it was significant, on average, 1.9 times higher than the yields of spring rapeseed sown from 3 May to 7 June. Meteorological conditions had a stronger effect on the field emergence and yield components of spring rapeseed than the sowing date.

Beschreibung: Prevalence, impact on shellfish resources and interspecific, spatial, and temporal variabilities of domoic acid (DA) in bivalves from Galicia (NW Spain) have been studied based on more than 25 years of monitoring data. The maximum prevalence (samples in which DA was detected) (100%) and incidence (samples with DA levels above the regulatory limit) (97.4%) were recorded in Pecten maximus, and the minimum ones in Mytilus galloprovincialis (12.6 and 1.1%, respectively). The maximum DA concentrations were 663.9 mg kg−1 in P. maximus and 316 mg kg−1 in Venerupis corrugata. After excluding scallop P. maximus data, DA was found (prevalence) in 13.3% of bivalve samples, with 1.3% being over the regulatory limit. In general, the prevalence of this toxin decreased towards the North but not the magnitude of its episodes. The seasonal distribution was characterized by two maxima, in spring and autumn, with the later decreasing in intensity towards the north. DA levels decreased slightly over the studied period, although this decreasing trend was not linear. A cyclic pattern was observed in the interannual variability, with cycles of 4 and 11 years. Intoxication and detoxification rates were slower than those expected from laboratory experiments, suggesting the supply of DA during these phases plays an important role.

Beschreibung: Determining biomarkers and better characterizing the biochemical progression of nonalcoholic fatty liver disease (NAFLD) remains a clinical challenge. A targeted 1H-NMR study of serum, combined with clinical variables, detected and localized biomarkers to stages of NAFLD in morbidly obese females. Pre-surgery serum samples from 100 middle-aged, morbidly obese female subjects, grouped on gold-standard liver wedge biopsies (non-NAFLD; steatosis; and fibrosis) were collected, extracted, and analyzed in aqueous (D2O) buffer (1H, 600 MHz). Profiled concentrations were subjected to exploratory statistical analysis. Metabolites varying significantly between the non-NAFLD and steatosis groups included the ketone bodies 3-hydroxybutyrate (↓; p = 0.035) and acetone (↓; p = 0.012), and also alanine (↑; p = 0.004) and a putative pyruvate signal (↑; p = 0.003). In contrast, the steatosis and fibrosis groups were characterized by 2-hydroxyisovalerate (↑; p = 0.023), betaine (↓; p = 0.008), hypoxanthine (↓; p = 0.003), taurine (↓; p = 0.001), 2-hydroxybutyrate (↑; p = 0.045), 3-hydroxyisobutyrate (↑; p = 0.046), and increasing medium chain fatty acids. Exploratory classification models with and without clinical variables exhibited overall success rates ca. 75–85%. In the study conditions, inhibition of fatty acid oxidation and disruption of the hepatic urea cycle are supported as early features of NAFLD that continue in fibrosis. In fibrosis, markers support inflammation, hepatocyte damage, and decreased liver function. Complementarity of NMR concentrations and clinical information in classification models is shown. A broader hypothesis that standard-of-care sera can yield metabolomic information is supported.

Beschreibung: In this study, the effects of supplemented inositol on sperm extenders were examined on the spermatozoa motility rate and duration, total antioxidant and oxidant status, apoptotic spermatozoa and DNA damage, during the sperm post-thaw process of Mesopotamian Catfish (Silurus triostegus, H. 1843). The semen was frozen in diluents containing different inositol concentrations (5, 10, 20 and 40 mg). Increasing levels of inositol linearly improved the spermatozoa motility rate and duration significantly (p 〈 0.05). MDA and TOS were linearly decreased, however, TAS and GSH linearly increased (p 〈 0.05). The increasing inositol levels resulted in a linear and quadratic decrease in DNA damage in the comet assay, 8-hydroxydeoxyguanosine and the determined percentage of apoptotic spermatozoa (p 〈 0.05). These results suggest that there are many positive effects of the use of supplemental inositol on enhancing sperm cryopreservation efficiency in Silurus triostegus.

Beschreibung: The purpose of the research was the recognition of edge effects regarding similarities and differences of vascular flora in undergrowth layers in the urban forest ecotones. Four types of urban forest neighborhoods were analyzed: ecotones adjacent to the manor park, the agriculture field, housing estates and the road. The plant compositions in the forest ecotones were compared with the plant compositions in the urban forest interior and the forest nature reserve. The phytosociological type of studied forests was a subcontinental oak-hornbeam one (Tilio-Carpinetum). Diagnostic plant species (e.g., characteristic) for forests from the non-diagnostic ones were identified. Forest consistent plant species dominated in the ecotone adjacent to the manor park and in the interior of urban forests too, but the best conditions for these plants were inside the forest nature reserve, where native consistent forest plants showed the highest dominance when comparing all studied areas. A higher anthropogenic pressure from the adjacent areas results in supporting the growth of inconsistent plant species in the forests, and these plants are mostly represented by plants belonging to grass and synanthropic communities. Another conclusion drawn from our research is that the protected forest, represented by a nature reserve in the city, provides better “shelter” for native forest plants than the urban forest without any protection. Ultimately, a permanent challenge is to achieve and maintain the balance between nature and the impact of anthropogenic activities on urban forests in the city. The high quality of green areas, biodiversity, including forests, implicates possibilities of sustainable development in cities. The research results will be useful for local urban planners and ecologists during their work on strategies of city development, including shaping of green infrastructure.

Beschreibung: The tree tomato (Solanum betaceum Cav.) is an underutilized fruit crop native to the Andean region and phylogenetically related to the tomato and potato. Tree tomato fruits have a high amount of nutrients and bioactive compounds. However, so far there are no studies at the genome or transcriptome level for this species. We performed a de novo assembly and transcriptome annotation for purple-fruited (A21) and an orange-fruited (A23) accessions. A total of 174,252 (A21) and 194,417 (A23) transcripts were assembled with an average length of 851 and 849 bp. A total of 34,636 (A21) and 36,224 (A23) transcripts showed a significant similarity to known proteins. Among the annotated unigenes, 22,096 (A21) and 23,095 (A23) were assigned to the Gene Ontology (GO) term and 14,035 (A21) and 14,540 (A23) were found to have Clusters of Orthologous Group (COG) term classifications. Furthermore, 22,096 (A21) and 23,095 (A23) transcripts were assigned to 155 and 161 (A23) KEGG pathways. The carotenoid biosynthetic process GO terms were significantly enriched in the purple-fruited accession A21. Finally, 68,647 intraspecific single-nucleotide variations (SNVs) and almost 2 million interspecific SNVs were identified. The results of this study provide a wealth of genomic data for the genetic improvement of the tree tomato.

Beschreibung: Permafrost is a key element of the cryosphere and sensitive to climate change. High-resolution permafrost map is important to environmental assessment, climate modeling, and engineering application. In this study, to estimate high-resolution Xing’an permafrost map (up to 1 km2), we employed the surface frost number (SFN) model and ground temperature at the top of permafrost (TTOP) model for the 2001–2018 period, driven by remote sensing data sets (land surface temperature and land cover). Based on the comparison of the modeling results, it was found that there was no significant difference between the two models. The performances of the SFN model and TTOP model were evaluated by using a published permafrost map. Based on statistical analysis, both the SFN model and TTOP model efficiently estimated the permafrost distribution in Northeast China. The extent of Xing’an permafrost distribution simulated by the SFN model and TTOP model were 6.88 × 105 km2 and 6.81 × 105 km2, respectively. Ground-surface characteristics were introduced into the permafrost models to improve the performance of models. The results provided a basic reference for permafrost distribution research at the regional scale.

Beschreibung: There is not any diet recommended for Hashimoto’s disease, despite that those patients are often undernourished. Because of the high heterogeneity of Hashimoto’s patients, insight into dietary patterns might shed some light on the patient-tailored dietary approach, thus improving their treatment and helping to identify patients with the highest probability of particular nutritional deficiencies. The aim of this study was to identify Hashimoto’s patients’ dietary patterns and their characterization based on both socio-demographic variables and dietary self-assessment. We collected data online from patients with Hashimoto’s disease. The questionnaire formula used in the study was developed based on a validated food frequency questionnaire KomPAN®. K-means pattern analyses were used to characterize patients into patterns based on the frequency of particular types of foods consumption and socio-demographic factors. Four patterns were identified. We labeled them as ‘Convenient’, ‘Non-meat’, ‘Pro-healthy’, and ‘Carnivores’ with participants proportions at approximately one-fourth per each pattern. The patients were mainly of the female gender (94.08%), with a female: male ratio of 15.9. Hashimoto’s patients differed in their food product choices, food choice motives, dieting experience, nutritional knowledge, smoking habits, food allergies and intolerances, and lipid disorders, and thus represent different eating patterns. However, these patterns were not determined by comorbidities or the majority of ailments.

Beschreibung: Blastocystis sp. is an important zoonotic protist in humans and various animals with worldwide distribution. However, there have been no data on the occurrence of Blastocystis sp. in C. bactrianus, an important economic animal in northwestern China. In the present study, a PCR-sequencing tool based on the SSU rRNA gene was applied to investigate the prevalence and genetic diversity of Blastocystis sp. in 638 faecal samples from C. bactrianus in 21 sampling sites within three main breeding areas (Gansu, Inner Mongolia and Xinjiang) in northwestern China. The total prevalence of Blastocystis sp. was 21.8% (139/638) in C. bactrianus, with the infection rates of 29.5% (18/61), 50.0% (14/28) and 19.5% (107/549) for animals aged 6 years, respectively. Significant differences in prevalence were detected among C. bactrianus from three geographic areas (χ2 = 19.972, df = 2, p 〈 0.001) and all sampling sites (χ2 = 104.154, df = 20, p 〈 0.001). A total of 16 of 21 sampling sites were positive for Blastocystis sp., with the prevalence ranging from 7.7% to 70.6%. Sequence analysis of the SSU rRNA gene identified eight subtypes in C. bactrianus in the present study, including seven animal adapted subtypes (ST10, ST14, ST21, ST24, ST25, ST26 and ST30) and one potentially novel subtype, with ST10 being the dominant one. To the best of our knowledge, this study provides the first insight for the occurrence and genetic make-up of Blastocystis sp. in C. bactrianus and contributes to the understanding of the transmission of Blastocystis infection in C. bactrianus in China.

Beschreibung: Regional climate change assessments show a likely temperature increase that is higher than the global average for all seasons in Africa, which would have extreme negative implications for ecosystem health and productivity. Most extreme climate change effects in West Africa are predicted to occur in desert and grassland areas. It is important for smallholder farmers in this region to understand the implications of these projections to their livelihood and to identify appropriate adaptation strategies. A grazing game was used to explore gender-specific adaptive responses to climate variability in the semiarid region of Ghana. The game was designed to understand the decision-making processes that result in the overgrazing of animals, leading to desertification based on the players’ interactions with the environment. A total of 44 grazing games comprising 22 games for male-headed households (HH) and 22 games for female-HH were played from August to December 2014 from 14 communities within the Bolgatanga Municipality and the Bongo district. The study revealed that males migrate to the southern part of the country to work on other people’s farms during the dry season as an adaptation strategy, while females engage in off-farm activities such as shea-butter production and basketry. Results of the game showed that males produced the highest number of cattle but created the largest desert patches. Females, on the other hand, were more conscious about the environment (long-term condition of the rangeland) than the short-term income benefits from the sale of cattle; hence, they created fewer desert patches. Strategies such as reducing the number of cattle to allow for the re-growth of vegetation in periods of feed scarcity, ploughing for one another using bulls, and family support using income from the sale of livestock were employed by both gender groups. The involvement of female farmers in decision-making is crucial to improve natural resource management.

Beschreibung: Overweight can be an additional problem in patients admitted to hospital. Objective: To analyze gender differences in pre-admission dietary habits and physical exercise and in HRQoL at hospital discharge among hospitalized adults with overweight. Methods: Cross-sectional study in non-diabetic patients enrolled in a clinical trial with body mass index (BMI) ≥ 25 Kg/m2 at admission. Bivariate analyses used Pearson’s chi-square test and Fisher’s exact test for qualitative variables and the Mann–Whitney test for numerical variables. Results: The study included 148 males and 127 females. At admission, women had higher BMI (p = 0.016) than men and a larger percentage consumed drugs for depression (p = 0.030) and anxiety (p = 0.049), and followed a religion-based diet (p = 0.022). Pre-admission, women had healthier habits related to dietary caloric intake (p = 0.009) and greater adherence to recommendations for a healthy diet (p = 0.001). At discharge, women described worse self-perceived health (p = 0.044) and greater pain/discomfort (p = 0.004) in comparison to men. Conclusions: Pre-admission, women had better habits related to a healthy diet and did not differ from men in habits related to physical exercise but had a higher BMI. At discharge, women reported worse self-perceived health and greater pain/discomfort. These differences should be considered for the adequate clinical management of patients with overweight.

Beschreibung: Normal brain function highly relies on the appropriate functioning of astrocytes. These glial cells are strategically situated between blood vessels and neurons, provide significant substrate support to neuronal demand, and are sensitive to neuronal activity and energy-related molecules. Astrocytes respond to many metabolic conditions and regulate a wide array of physiological processes, including cerebral vascular remodeling, glucose sensing, feeding, and circadian rhythms for the control of systemic metabolism and behavior-related responses. This regulation ultimately elicits counterregulatory mechanisms in order to couple whole-body energy availability with brain function. Therefore, understanding the role of astrocyte crosstalk with neighboring cells via the release of molecules, e.g., gliotransmitters, into the parenchyma in response to metabolic and neuronal cues is of fundamental relevance to elucidate the distinct roles of these glial cells in the neuroendocrine control of metabolism. Here, we review the mechanisms underlying astrocyte-released gliotransmitters that have been reported to be crucial for maintaining homeostatic regulation of systemic metabolism.

Beschreibung: Community-based rehabilitation (CBR) is a multi-sectorial community strategy for guaranteeing that people with disabilities enjoy the same rights and opportunities as all other community members. CBR is organized in a five-component matrix—namely, health, education, social, livelihood, and empowerment. To measure the effectiveness of CBR, the World Health Organization (WHO) has developed standardized indicators. The objective of the present study is to translate and validate the CBR indicators (CBR-Is), providing preliminary evidence of their use for disability in Italy. After obtaining permission from the WHO, the CBR-Is followed a process of translation and cross-cultural adaptation according to international guidelines. An examination of internal consistency and reliability was than performed. The intra-rater reliability was estimated using the Intraclass Correlation Coefficient with a 95% confidence interval. In order to measures the differences between people with and without disabilities, an independent sample t-test was used for quantitative indicators. The Italian version of the CBR-Is (IT-CBR-Is) was administered to 234 people. The internal consistency showed a good value, with a Cronbach’s alpha coefficient of 0.862, and the intra-rater reliability analysis showed solid values for each domain (range: 0.723–0.882). Statistically significant differences between people with and without disabilities were found for each domain of the CBR matrix—namely, health, social, education, livelihood, and empowerment. The IT-CBR-Is are consistent and reliable measures when used to investigate disability in a community-based inclusive development perspective. National stakeholders can now have specific indicators to implement services and actions for people with disabilities.

Beschreibung: Smoke-free pregnancies have long-term health benefits for mothers and babies. This paper quantitatively examines factors associated with smoke-free pregnancies among Aboriginal and Torres Strait Islander women (hereafter Aboriginal women) and qualitatively explores their smoking cessation (SC) experiences during pregnancy. An Aboriginal-led online cross-sectional study on SC was conducted with Aboriginal women and in partnership with Aboriginal communities, between July and October 2020. The present analysis includes participants who made a pregnancy-related quit attempt (N = 103). Chi-squared tests, logistic regression models, and thematic analysis of free-form text responses were performed. The adjusted odds of having smoke-free pregnancies were 4.54 times higher among participants who used Aboriginal Health Services (AHS) (AOR = 4.54, p-value 0.018). Participants living in urban settings had 67% lower odds of having smoke-free pregnancies compared to their regional/remote counterparts (AOR = 0.33, p-value 0.020). Qualitative data revealed strong motivations to reduce tobacco-related harms to the fetus and variability in quitting experiences at different stages of and across pregnancies. Smoking cessation care (SCC) can support Aboriginal women meaningfully if their quitting experiences are considered in SCC development and implementation. Consistent funding for AHS-led SCC is needed to garner health benefits for Aboriginal peoples. More research into urban versus regional/remote differences in maternal SC is recommended.

Beschreibung: Calmodulin (CaM), as an important factor in the calcium signaling pathway, is widely involved in plant growth and development regulation and responses to external stimuli. In this study, the full-length sequence of the ScCaM gene (GenBank: GQ246454) was isolated from the leaves of a Saccharum spp. hybrid. Prokaryotic expression showed that ScCaM could be solubly expressed and purified in Escherichia coli BL21. Subcellular localization confirmed that ScCaM was localized in the plasma membrane and nucleus of cells. A quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed that ScCaM can be induced by various stresses, including sodium chloride (NaCl), chromium trichloride (CrCl3), salicylic acid (SA), and methyl jasmonate (MeJA). Ectopic expression in Arabidopsis thaliana demonstrated that ScCaM can affect the growth and development of transgenic plants. Moreover, the qRT-PCR analysis indicated that the overexpression of the allogenic ScCaM gene inhibits the expression of AtSTM, leading to the phenomenon of multiple-tillering in transgenic A. thaliana. The present study provided valuable information and facilitates further investigation into the function of ScCaM in the future.

Beschreibung: Individual identification plays an important part in disease prevention and control, traceability of meat products, and improvement of agricultural false insurance claims. Automatic and accurate detection of cattle face is prior to individual identification and facial expression recognition based on image analysis technology. This paper evaluated the possibility of the cutting-edge object detection algorithm, RetinaNet, performing multi-view cattle face detection in housing farms with fluctuating illumination, overlapping, and occlusion. Seven different pretrained CNN models (ResNet 50, ResNet 101, ResNet 152, VGG 16, VGG 19, Densenet 121 and Densenet 169) were fine-tuned by transfer learning and re-trained on the dataset in the paper. Experimental results showed that RetinaNet incorporating the ResNet 50 was superior in accuracy and speed through performance evaluation, which yielded an average precision score of 99.8% and an average processing time of 0.0438 s per image. Compared with the typical competing algorithms, the proposed method was preferable for cattle face detection, especially in particularly challenging scenarios. This research work demonstrated the potential of artificial intelligence towards the incorporation of computer vision systems for individual identification and other animal welfare improvements.

Beschreibung: Dietary fibre has proven to promote healthy body mass and reduce the risk of non-communicable diseases. To date, in Slovenia, there were only a few outdated studies of dietary fibre intake; therefore, we explored the dietary fibre intake using food consumption data collected in the SI.Menu project. Following the EU Menu methodology, data were collected on representative samples of adolescents, adults, and elderlies using a general questionnaire, a food propensity questionnaire, and two 24 h recalls. The results indicate that the intake of dietary fibre in Slovenia is lower than recommended. The proportion of the population with inadequate fibre intakes (

Beschreibung: This study aimed to determine the prevalence of high levels of knowledge, positive attitude, and good practice on evidence-based medicine (EBM) and identify the associated factors for practice score on EBM among emergency medicine doctors in Kelantan, Malaysia. This cross-sectional study was conducted in government hospitals in Kelantan. The data were collected from 200 emergency physicians and medical officers in the emergency department using the Noor Evidence-Based Medicine Questionnaire. Simple and general linear regressions analyses using SPSS were performed. A total of 183 responded, making a response rate of 91.5%. Of them, 49.7% had a high level of knowledge, 39.9% had a positive attitude and 2.1% had good practice. Sex, race, the average number of patients seen per day, internet access in workplace, having online quick reference application, and attitude towards EBM were significantly associated with EBM practice scores. It is recommended that appropriate authorities provide emergency doctors with broader access to evidence resources. EBM skill training should be enhanced in the current medical school curriculums.

Beschreibung: The present study aimed at assessing the consequences of prolonged exposure to COVID-19 distress on mental health in non-frontline health care workers. For this purpose, we have conducted a survey on 425 Italian dermatologists, in the period February–March 2021. The psychopathological symptoms, depression, anxiety, post-traumatic stress symptoms (PTSD), as well as resilience, have been evaluated. The main factors that influence the physician’s psychological health have been also investigated. Our study showed that the physicians older than 40 years, as well as those who lived this period in company, reported more personal resources, better managing the distress. Resilience, COVID-19 belief, COVID-19 working difficulties, and age were the common predictors of the severe psychopathological symptoms. An interesting result is that the lower level of resilience was the most powerful predictor of a more severe depression, as well as of a higher severity of generalized anxiety disorder, but not of COVID-19 PTSD. The fear of COVID-19 was the most powerful predictor of COVID-19 PTSD. Home conditions and previous SARS-CoV2 infection constituted significant predictors of severe depressive symptoms, but not of anxiety and COVID-19 PTSD. These results are useful in a better understanding of protective and risk factors involved in COVID-19 long-term distress exposure.

Beschreibung: The generation of a comprehensive catalog of null alleles covering all protein-coding genes is the goal of the International Mouse Phenotyping Consortium. Over the past 20 years, significant progress has been made towards achieving this goal through the combined efforts of many large-scale programs that built an embryonic stem cell resource to generate knockout mice and more recently employed CRISPR/Cas9-based mutagenesis to delete critical regions predicted to result in frameshift mutations, thus, ablating gene function. The IMPC initiative builds on prior and ongoing work by individual research groups creating gene knockouts in the mouse. Here, we analyze the collective efforts focusing on the combined null allele resource resulting from strains developed by the research community and large-scale production programs. Based upon this pooled analysis, we examine the remaining fraction of protein-coding genes focusing on clearly defined mouse–human orthologs as the highest priority for completing the mutant mouse null resource. In summary, we find that there are less than 3400 mouse–human orthologs remaining in the genome without a targeted null allele that can be further prioritized to achieve our overall goal of the complete functional annotation of the protein-coding portion of a mammalian genome.

Beschreibung: Bearing in mind the growing interest in Yerba Mate, a comprehensive study has been prepared containing the most important aspects and possibilities of its use. The introduction of the work contains the species characteristics of Yerba Mate, as well as information about the origin and places of cultivation. The next part focuses on the analysis of the composition, pointing to purine alkaloids, polyphenols, saponins, and minerals as groups of active compounds responsible for the clinical activity of Yerba Mate. The review of the results of preclinical and clinical studies indicates activity in relation to the stimulating effect, reducing weight by stimulating lipolysis, cardioprotective, anti-diabetic, and anti-inflammatory effects. The information about the action of Yerba Mate is supplemented by the characteristics of its potential toxicity in terms of PAHs content (in particular benzo[α]pyrene) and preparation as a determinant of increased irritation. The current data on the effects of Yerba Mate and the wide safety margin of its use position this raw material as a valuable component of functional food. The growing frequency of consuming Yerba Mate, conditioned by the availability resulting from the globalization of the market and the information provided about it’s the pro-health effects, will position Yerba Mate’s popularity among wider population groups.

Beschreibung: The colonization of Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), has a detrimental effect on the respiratory care of pediatric patients with cystic fibrosis (CF). In addition to being resistant to multiple antibiotics, S. aureus also has the ability to form biofilms, which makes the infection more difficult to treat and eradicate. In this study, we examined the ability of S. aureus strains isolated from pediatric patients with CF to form biofilms. We screened a transposon mutant library of MRSA and identified a putative cobalt transporter ATP binding domain (cbiO) that is required for biofilm formation. We discovered that deleting cbiO creating a cbiO null mutant in CFSa36 (an MRSA strain isolated from a patient with cystic fibrosis) significantly hinders the ability of CFSa36 to form biofilm. The complementation of cbiO restored the ability of the cbiO deletion mutant to generate biofilm. Interestingly, we revealed that incorporating extra copper ions to the chemically defined medium (CDM) complemented the function of cbiO for biofilm formation in a dose-dependent manner, while the addition of extra iron ions in CDM enhanced the effect of cbiO null mutation on biofilm formation. In addition, neither the addition of certain extra amounts of copper ions nor iron ions in CDM had an impact on bacterial growth. Taken together, our findings suggest that cbiO mediates biofilm formation by affecting the transportation of copper ions in the MRSA CFSa36 strain. This study provides new insights into the molecular basis of biofilm formation by S. aureus.

Beschreibung: Canine angiostrongylosis by Angiostrongylus vasorum is increasingly reported in both enzootic and previously free areas. The complex pathogenesis of the disease makes the clinical workup challenging. Infected dogs show highly variable clinical pictures, characterized by subclinical to life-threatening general, cardio-respiratory, neurological and/or gastrointestinal signs. The present study reports the high variability of clinical pictures from 36 dogs across central and southern Italy that were naturally infected by A. vasorum. Of them, 23 (63.9%) presented at least one clinical sign, while 13 (36.1%) were subclinically infected and apparently healthy. Overall, 19 dogs (52.8%) showed cardiorespiratory signs, 14 (38.9%) had non-specific abnormalities, 2 (5.6%) presented coagulation disorders and 1 (2.8%) had a severe neurological condition. Importantly, four dogs presenting with clinical signs had neither cough nor dyspnea. These results underline that angiostrongylosis should be included in the differential diagnosis, even when dogs display only non-specific clinical signs. The proportion of apparently healthy dogs highlights the relevance of routine copromicroscopic and/or antigenic tests in enzootic areas to avoid the sudden onset of potentially life-threatening signs.

Beschreibung: Climate change, increasing environmental pollution, continuous loss of biodiversity, and a growing human population with increasing food demand, threaten the functioning of agro-ecosystems and their contribution to people and society. Agroforestry systems promise a number of benefits to enhance nature’s contributions to people. There are a wide range of agroforestry systems implemented representing different levels of establishment across the globe. This range and the long time periods for the establishment of these systems make empirical assessments of impacts on ecosystem functions difficult. In this study we investigate how simulation models can help to assess and predict the role of agroforestry in nature’s contributions. The review of existing models to simulate agroforestry systems reveals that most models predict mainly biomass production and yield. Regulating ecosystem services are mostly considered as a means for the assessment of yield only. Generic agroecosystem models with agroforestry extensions provide a broader scope, but the interaction between trees and crops is often addressed in a simplistic way. The application of existing models for agroforestry systems is particularly hindered by issues related to code structure, licences or availability. Therefore, we call for a community effort to connect existing agroforestry models with ecosystem effect models towards an open-source, multi-effect agroforestry modelling framework.

Beschreibung: H5N1 COBRA hemagglutinin (HA) sequences, termed human COBRA-2 HA, were constructed through layering of HA sequences from viruses isolated from humans collected between 2004–2007 using only clade 2 strains. These COBRA HA proteins, when expressed on the surface of virus-like particles (VLP), elicited protective immune responses in mice, ferrets, and non-human primates. However, these vaccines were not as effective at inducing neutralizing antibodies against newly circulating viruses. Therefore, COBRA HA-based vaccines were updated in order to elicit protective antibodies against the current circulating clades of H5Nx viruses. Next-generation COBRA HA vaccines were designed to encompass the newly emerging viruses circulating in wild avian populations. HA amino acid sequences from avian and human H5 influenza viruses isolated between 2011–2017 were downloaded from the GISAID (Global Initiative on Sharing All Influenza Data). Mice were vaccinated with H5 COBRA rHA that elicited antibodies with hemagglutinin inhibition (HAI) activity against H5Nx viruses from five clades. The H5 COBRA rHA vaccine, termed IAN8, elicited protective immune responses against mice challenged with A/Sichuan/26621/2014 and A/Vietnam/1203/2004. This vaccine elicited antibodies with HAI activity against viruses from clades 2.2, 2.3.2.1, 2.3.4.2, 2.2.1 and 2.2.2. Lungs from vaccinated mice had decreased viral titers and the levels of cellular infiltration in mice vaccinated with IAN-8 rHA were similar to mice vaccinated with wild-type HA comparator vaccines or mock vaccinated controls. Overall, these next-generation H5 COBRA HA vaccines elicited protective antibodies against both historical H5Nx influenza viruses, as well as currently circulating clades of H5N1, H5N6, and H5N8 influenza viruses.

Beschreibung: Eight pens (25 pigs/pen; n = 200) provided with an interactive straw-filled rooting tower (experimental group) and five pens (25 pigs/pen; n = 125) with a stationary (fixed) tower without straw (control group) were compared within three fattening periods on a conventional farm with fully slatted flooring. The effectiveness of the tower to trigger favourable behaviour in feeding and outside feeding periods was assessed. The incidence of deep tail injuries was lower in the experimental group (experimental group: Odds Ratio 0.3, p 〈 0.001) and was influenced by the batch (Odds Ratio: 2.38, p 〈 0.001) but not by pen and sex. In spring, most pens were excluded due to severe tail biting. Tail injury scores were more severe in the control group in weeks 5, 6 and 7 compared to the experimental group (p = 0.002, p 〈 0.001, p 〈 0.001, respectively). Tower manipulation was more frequent during feeding compared to outside feeding time (p = 0.002). More head than tail manipulation occurred in the experimental group (p = 0.03). The interactive tower as the only measure was not appropriate to reduce tail biting sufficiently in pigs with intact tails on a conventional fattening farm. Of high priority to prevent tail biting outbreaks was the early detection of biting pigs.

Beschreibung: Accumulation of misfolded proteins in ER activates the unfolded protein response (UPR), a multifunctional signaling pathway that is important for cell survival. The UPR is regulated by three ER transmembrane sensors, one of which is inositol-requiring protein 1 (IRE1). IRE1 activates a transcription factor, X-box-binding protein 1 (XBP1), by removing a 26-base intron from XBP1 mRNA that generates spliced XBP1 mRNA (XBP1s). To search for XBP1 transcriptional targets, we utilized an XBP1s-inducible human cell line to limit XBP1 expression in a controlled manner. We also verified the identified XBP1-dependent genes with specific silencing of this transcription factor during pharmacological ER stress induction with both an N-linked glycosylation inhibitor (tunicamycin) and a non-competitive inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) (thapsigargin). We then compared those results to the XBP1s-induced cell line without pharmacological ER stress induction. Using next‐generation sequencing followed by bioinformatic analysis of XBP1-binding motifs, we defined an XBP1 regulatory network and identified XBP1 as a repressor of PUMA (a proapoptotic gene) and IRE1 mRNA expression during the UPR. Our results indicate impairing IRE1 activity during ER stress conditions accelerates cell death in ER-stressed cells, whereas elevating XBP1 expression during ER stress using an inducible cell line correlated with a clear prosurvival effect and reduced PUMA protein expression. Although further studies will be required to test the underlying molecular mechanisms involved in the relationship between these genes with XBP1, these studies identify a novel repressive role of XBP1 during the UPR.

Beschreibung: In Japan, there is concern regarding the relation between the inappropriate use of antibiotics and antibiotic resistance (AMR). Increased bacterial resistance is due in part to the inappropriate use of antimicrobial agents. The support of the pharmacist becomes important, and there is growing interest in antimicrobial stewardship to promote the appropriate and safe use of antimicrobials needed for the optimal selection of drugs, doses, durations of therapy, therapeutic drug monitoring (TDM), and implementations of cost containment strategies in Japan. Pharmacists should strive to disseminate the concept of “choosing wisely” in relation to all medicines, implement further interventions, and put them into practice. In this article, we present data for antimicrobial stewardship and Japan’s AMR action plan, focusing on how pharmacists should be involved in enabling physicians to choose antimicrobials wisely.

Beschreibung: The study aimed to evaluate the changes in the quantitative composition of a soil bacterial community near a municipal waste landfill, and attempted to use a bacteriological coefficient to assess the degree of soil degradation. The research was carried out near a landfill site located in southern Poland. Soil samples were collected from plots on which spring wheat, field bean and potato were cultivated. Microbiological analyses included the determination of the total number of bacteria in active and dormant (sporulating) stages. The highest ratio of sporulating bacteria in relation to vegetative bacteria was found in the reclaimed sector of the landfill site. The proposed bacteriological indicator of soil quality (i.e., the ratio of the number of sporulating bacteria to the number of vegetative forms) seems to be a good index for the assessment of soil quality near the landfill site.

Beschreibung: Rare earth elements (REEs) are key constituents of modern technology and play important roles in various chemical and industrial applications. They also are increasingly used in agricultural and zootechnical applications, such as fertilizers and feed additives. Early applications of REEs in agriculture have originated in China over the past several decades with the objective of increasing crop productivity and improving livestock yield (e.g., egg production or piglet growth). Outside China, REE agricultural or zootechnical uses are not currently practiced. A number of peer-reviewed manuscripts have evaluated the adverse and the positive effects of some light REEs (lanthanum and cerium salts) or REE mixtures both in plant growth and in livestock yield. This information was never systematically evaluated from the growing body of scientific literature. The present review was designed to evaluate the available evidence for adverse and/or positive effects of REE exposures in plant and animal biota and the cellular/molecular evidence for the REE-associated effects. The overall information points to shifts from toxic to favorable effects in plant systems at lower REE concentrations (possibly suggesting hormesis). The available evidence for REE use as feed additives may suggest positive outcomes at certain doses but requires further investigations before extending this use for zootechnical purposes.

Beschreibung: Several X-linked genes are involved in neuronal differentiation and may contribute to the generation of sex dimorphisms in the brain. Previous results showed that XX hypothalamic neurons grow faster, have longer axons, and exhibit higher expression of the neuritogenic gene neurogenin 3 (Ngn3) than XY before perinatal masculinization. Here we evaluated the participation of candidate X-linked genes in the development of these sex differences, focusing mainly on Kdm6a, a gene encoding for an H3K27 demethylase with functions controlling gene expression genome-wide. We established hypothalamic neuronal cultures from wild-type or transgenic Four Core Genotypes mice, a model that allows evaluating the effect of sex chromosomes independently of gonadal type. X-linked genes Kdm6a, Eif2s3x and Ddx3x showed higher expression in XX compared to XY neurons, regardless of gonadal sex. Moreover, Kdm6a expression pattern with higher mRNA levels in XX than XY did not change with age at E14, P0, and P60 in hypothalamus or under 17β-estradiol treatment in culture. Kdm6a pharmacological blockade by GSK-J4 reduced axonal length only in female neurons and decreased the expression of neuritogenic genes Neurod1, Neurod2 and Cdk5r1 in both sexes equally, while a sex-specific effect was observed in Ngn3. Finally, Kdm6a downregulation using siRNA reduced axonal length and Ngn3 expression only in female neurons, abolishing the sex differences observed in control conditions. Altogether, these results point to Kdm6a as a key mediator of the higher axogenesis and Ngn3 expression observed in XX neurons before the critical period of brain masculinization.

Beschreibung: The majority of colorectal cancer (CRC) patients carry mutations in the APC gene, which lead to the unregulated activation of the Wnt pathway. Extracellular vesicles (EV) are considered potential therapeutic tools. Although CRC is a genetically heterogeneous disease, the significance of the intra-tumor heterogeneity in EV uptake of CRC cells is not yet known. By using mouse and patient-derived organoids, the currently available best model of capturing cellular heterogeneity, we found that Apc mutation induced the expression of interferon-induced transmembrane protein 1 (Ifitm1), a membrane protein that plays a major role in cellular antiviral responses. Importantly, organoids derived from IFITM1high CRC cells contained more proliferating cells and they had a markedly reduced uptake of fibroblast EVs as compared to IFITM1low/− cells. In contrast, there was no difference in the intensity of EV release between CRC subpopulations with high and low IFITM1 levels. Importantly, the difference in cell proliferation between these two subpopulations disappeared in the presence of fibroblast-derived EVs, proving the functional relevance of the enhanced EV uptake by IFITM1low CRC cells. Furthermore, inactivating IFITM1 resulted in an enhanced EV uptake, highlighting the importance of this molecule in establishing the cellular difference for EV effects. Collectively, we identified CRC cells with functional difference in their EV uptake ability that must be taken into consideration when using EVs as therapeutic tools for targeting cancer cells.

Beschreibung: Cartilage has little intrinsic capacity for repair, so transplantation of exogenous cartilage cells is considered a realistic option for cartilage regeneration. We explored whether human-induced pluripotent stem cells (hiPSCs) could represent such unlimited cell sources for neo-cartilage comparable to human primary articular chondrocytes (hPACs) or human bone marrow-derived mesenchymal stromal cells (hBMSCs). For this, chondroprogenitor cells (hiCPCs) and hiPSC-derived mesenchymal stromal cells (hiMSCs) were generated from two independent hiPSC lines and characterized by morphology, flow cytometry, and differentiation potential. Chondrogenesis was compared to hBMSCs and hPACs by histology, immunohistochemistry, and RT-qPCR, while similarities were estimated based on Pearson correlations using a panel of 20 relevant genes. Our data show successful differentiations of hiPSC into hiMSCs and hiCPCs. Characteristic hBMSC markers were shared between hBMSCs and hiMSCs, with the exception of CD146 and CD45. However, neo-cartilage generated from hiMSCs showed low resemblances when compared to hBMSCs (53%) and hPACs (39%) characterized by lower collagen type 2 and higher collagen type 1 expression. Contrarily, hiCPC neo-cartilage generated neo-cartilage more similar to hPACs (65%), with stronger expression of matrix deposition markers. Our study shows that taking a stepwise approach to generate neo-cartilage from hiPSCs via chondroprogenitor cells results in strong similarities to neo-cartilage of hPACs within 3 weeks following chondrogenesis, making them a potential candidate for regenerative therapies. Contrarily, neo-cartilage deposited by hiMSCs seems more prone to hypertrophic characteristics compared to hPACs. We therefore compared chondrocytes derived from hiMSCs and hiCPCs with hPACs and hBMSCs to outline similarities and differences between their neo-cartilage and establish their potential suitability for regenerative medicine and disease modelling.

Beschreibung: Hepatocellular carcinoma (HCC) is one of the most difficult cancer types to treat. Liver cancer is often diagnosed at late stages and therapeutic treatment is frequently accompanied by development of multidrug resistance. This leads to poor outcomes for cancer patients. Understanding the fundamental molecular mechanisms leading to liver cancer development is crucial for developing new therapeutic approaches, which are more efficient in treating cancer. Mice with a liver specific UDP-glucose ceramide glucosyltransferase (UGCG) knockout (KO) show delayed diethylnitrosamine (DEN)-induced liver tumor growth. Accordingly, the rationale for our study was to determine whether UGCG overexpression is sufficient to drive cancer phenotypes in liver cells. We investigated the effect of UGCG overexpression (OE) on normal murine liver (NMuLi) cells. Increased UGCG expression results in decreased mitochondrial respiration and glycolysis, which is reversible by treatment with EtDO-P4, an UGCG inhibitor. Furthermore, tumor markers such as FGF21 and EPCAM are lowered following UGCG OE, which could be related to glucosylceramide (GlcCer) and lactosylceramide (LacCer) accumulation in glycosphingolipid-enriched microdomains (GEMs) and subsequently altered signaling protein phosphorylation. These cellular processes lead to decreased proliferation in NMuLi/UGCG OE cells. Our data show that increased UGCG expression itself does not induce pro-cancerous processes in normal liver cells, which indicates that increased GlcCer expression leads to different outcomes in different cancer types. Graphic abstract