Genetic diversity within leukemia-associated immunophenotype-defined subclones in AML

Acute myeloid leukemia (AML) is a highly heterogeneous disease showing dynamic clonal evolution patterns over time. Various subclones may be present simultaneously and subclones may show a different expansion pattern and respond differently to applied therapies. It is already clear that immunophenotyping and genetic analyses may yield overlapping, but also complementary information. Detailed information on the genetic make-up of immunophenotypically defined subclones is however scarce. We performed error-corrected sequencing for 27 myeloid leukemia driver genes in 86, FACS-sorted immunophenotypically characterized normal and aberrant subfractions in 10 AML patients. We identified three main scenarios. In the first group of patients, the two techniques were equally well characterizing the malignancy. In the second group, most of the isolated populations did not express aberrant immunophenotypes but still harbored several genetic aberrancies, indicating that the information obtained only by immunophenotyping would be incomplete. Vice versa, one patient was identified in which genetic mutations were found only in a small fraction of the immunophenotypically defined malignant populations, indicating that the genetic analysis gave an incomplete picture of the disease. We conclude that currently, characterization of leukemic cells in AML by molecular and immunophenotypic techniques is complementary, and infer that both techniques should be used in parallel in order to obtain the most complete view on the disease.

Estrogen Impairs Adipose Tissue Expansion and Cardiometabolic Profile in Obese-Diabetic Female Rats

It has been reported that 17β-estradiol (E2) can exert beneficial effects against the development of obesity, providing women with a healthier metabolic profile and conferring cardiovascular protection. However, a growing body of evidence questions this role in the context of obesity and diabetes. We focus on the adipose tissue–heart axis to address the question of whether E2 can have metabolically detrimental effects in an obese-diabetic rat model. Female Zucker Diabetic Fatty rats were used: LEAN, fa/+; SHAM, sham-operated fa/fa; OVA, ovariectomized fa/fa, and OVA+E2, ovariectomized and E2 treated fa/fa. The secretory expression profile, tissue expansion parameters and composition of visceral adipose tissue, as well as systemic and cardiac parameters related to insulin resistance, fibrosis, and inflammation were analyzed. Ovariectomy induced an attenuation of both diabetic condition and metabolic dysfunction of adipose tissue and cardiac muscle in fa/fa rats, suggesting that E2, in the context of diabetes and obesity, loses its cardioprotective role and could even contribute to greater metabolic alterations. Adipose tissue from OVA rats showed a healthier hyperplastic expansion pattern, which could help maintain tissue function, increase adiponectin expression, and decrease pro-inflammatory adipokines. These findings should be taken into account when considering hormone replacement therapy for obese-diabetic women.

Success and complication rate of miniscrew assisted non-surgical palatal expansion in adults - a consecutive study using a novel force-controlled polycyclic activation protocol

Introduction Bone-borne miniscrew assisted palatal expansion (MAPE) is a common technique to improve maxillary transverse deficiency in young adolescents. Adult patients usually present a challenge, as they often require additional surgical assisted maxillary expansion (SARPE). There is still no clear statement about non-surgical expansion in adult patients using this technique. The aim of this study was to evaluate the success and complication rate of non-surgical palatal expansion in adults utilizing MAPE with a novel force-controlled polycyclic expansion protocol (FCPC). Methods This consecutive study consisted of 33 adult patients with an average age of 29.1 ± 10.2 years (min. 18 years, max. 58 years), including one dropout patient. First, four miniscrews were inserted and after 12-weeks latency, the expander was placed and the FCPC protocol was applied (MAPE group). In case of missing expansion, a SARPE was performed (SARPE group). After maximum expansion, a cone beam CT was made and widening of the midpalatal suture was measured. The outcome variables were successful non-surgical expansion and, with sample size power above 80%, the odds of failed non-surgical expansion and associated complications were evaluated. The primary predictor variable was age. Statistical analysis was performed using R (Version 3.1) to calculate power, to construct various models for measuring the odds of requiring surgical intervention/complications, and others. Results Successful non-surgical expansion was achieved in 27 patients (84.4%), ranging from 18 to 49 years. Mean age differed significantly between both groups (26.8 ± 8.2 years vs. 41.3 ± 9.9 years; p < 0.001). Mean expansion at the anterior and posterior palate for the MAPE group was 5.4 ± 1.5 mm and 2.5 ± 1.1 mm, respectively. Among these subjects’ complications were observed in 18.5%. Age significantly increased the odds of complications (p = 0.019). Conclusions 1. The success rate of MAPE among individuals aged 18 to 49 years was 84.4%. 2. A V-shaped expansion pattern in the antero-posterior dimension was mostly observed. 3. Complications were significantly associated with age. 4. A careful expansion protocol seems to be beneficial to prevent unfavorable results in adult patients. Trial registration Consecutive cohort study, Review Board No. EK-2-2014/0016.

Nitrogen Assimilation Related Genes in Brassica napus: Systematic Characterization and Expression Analysis Identified Hub Genes in Multiple Nutrient Stress Responses

Nitrogen (N) is an essential macronutrient for plants. However, little is known about the molecular regulation of N assimilation in Brassica napus, one of the most important oil crops worldwide. Here, we carried out a comprehensive genome-wide analysis of the N assimilation related genes (NAGs) in B. napus. A total of 67 NAGs were identified encoding major enzymes involved in N assimilation, including asparagine synthetase (AS), glutamate dehydrogenase (GDH), glutamine oxoglutarate aminotransferase (GOGAT), glutamine synthetase (GS), nitrite reductase (NiR), nitrate reductase (NR). The syntenic analysis revealed that segmental duplication and whole-genome duplication were the main expansion pattern during gene evolution. Each NAG family showed different degrees of differentiation in characterization, gene structure, conserved motifs and cis-elements. Furthermore, diverse responses of NAG to multiple nutrient stresses were observed. Among them, more NAGs were regulated by N deficiency and ammonium toxicity than by phosphorus and potassium deprivations. Moreover, 12 hub genes responding to N starvation were identified, which may play vital roles in N utilization. Taken together, our results provide a basis for further functional research of NAGs in rapeseed N assimilation and also put forward new points in their responses to contrasting nutrient stresses.

Time-resolved, integrated analysis of clonal genome evolution in parthenogenetic animals and in cancer

Clonal genome evolution is a key aspect for parthenogenetic species and cancer. While many studies describe precise landscapes of clonal evolution in cancer, few studies determine the underlying evolutionary parameters from molecular data, and fewer integrate theory with data. We derived theoretical results linking mutation rate, time, expansion dynamics, transition to recurrence, and survival. With this, we inferred time-resolved estimates of evolutionary parameters from mutation accumulation, mutational signatures and selection. Using this framework we traced the speciation of the rapidly emerging and invasive marbled crayfish to a time window between 1947 and 1996, which is consistent with biological records. In glioblastoma samples, we determined tumor expansion patterns, and tumor cell survival ratio at resection. Interestingly, our results suggest that the expansion pattern in the primary tumor is predictive of the progress and time to recurrence. In addition, tumor cell survival was always higher after resection and was associated with the expansion pattern and time to recurrence. We further observed selection events in a subset of tumors, with longer and purifying-only selection phases in recurrent tumors. In conclusion, our framework allowed a time-resolved, integrated analysis of key parameters in clonally evolving genomes, and provided novel insights into the evolutionary age of marbled crayfish and the progression of glioblastoma.

Success And Complication Rate of Miniscrew Assisted Non-Surgical Palatal Expansion In Adults - A Consecutive Study Using A Novel Force-Controlled Polycyclic Activation Protocol

Introduction: Bone-borne miniscrew assisted palatal expansion (MAPE) is a common technique to improve maxillary transverse deficiency in young adolescents. Adult patients usually present a challenge, as they often require additional surgical assisted maxillary expansion (SARPE). There is still no clear statement about non-surgical expansion in adult patients using this technique. The aim of this study was to evaluate the success and complication rate of non-surgical palatal expansion in adults utilizing MAPE with a novel force-controlled polycyclic expansion protocol (FCPC).Methods: This consecutive study consisted of 33 adult patients with an average age of 29.1 ± 10.2 years (min. 18 years, max. 58 years), including one dropout patient. First, four miniscrews were inserted and after 12-weeks latency, the expander was placed and the FCPC protocol was applied (MAPE group). In case of missing expansion, a SARPE was performed (SARPE group). After maximum expansion, a cone beam CT was made and widening of the midpalatal suture was measured. The outcome variables were successful non-surgical expansion and, with sample size power above 80%, the odds of failed non-surgical expansion and associated complications were evaluated. The primary predictor variable was age. Statistical analysis was performed using R (Version 3.1) to calculate power, to construct various models for measuring the odds of requiring surgical intervention/complications, and others.Results: Successful non-surgical expansion was achieved in 27 patients (84.4%), ranging from 18 to 49 years. Mean age differed significantly between both groups (26.8 ± 8.2 years vs. 41.3 ± 9.9 years; p < 0.001). Mean expansion at the anterior and posterior palate for the MAPE group was 5.4 ± 1.5 mm and 2.5 ± 1.1 mm, respectively. Among these subjects' complications were observed in 18.5%. Age significantly increased the odds of complications (p = 0.019).Conclusions:1. The success rate of MAPE among individuals aged 18 to 49 years was 84.4%.2. A V-shaped expansion pattern in the antero-posterior dimension was mostly observed.3. Complications were significantly associated with age.4. A careful expansion protocol seems to be beneficial to prevent unfavorable results in adult patients.Trial registration: consecutive cohort study, Review Board No. EK-2-2014/0016

Monitoring Urban Expansion and Urban Green Spaces Change in Addis Ababa: Directional and Zonal Analysis Integrated with Landscape Expansion Index

Addis Ababa, the capital of Ethiopia, is urbanizing very fast. This study aimed to assess urban expansion and Urban Green Spaces (UGS) change in the city from 1989 to 2019. Remote Sensing and Geographical Information System (GIS) and Landscape Expansion Index (LEI) were used to extract Land Use Land Cover (LULC) data, measure urban expansion and UGS change and analyze urban growth pattern in inner zone, outer zone and eight quadrants. The results showed that urban area in the inner zone increased from 3712 ha to 3716 ha (0.1%), and from 3716 ha to 3874 ha (4.2%) and in the first (1989–1999) and second periods (1999–2009), while it decreased from 3874 ha to 3733 ha (3.6%) in the third period (2009–2019), portraying a non-unidirectional trend of change. Conversely, the UGS in the inner zone decreased from 60 ha to 54 ha (10%), and from 54 ha to 38 ha (29.6%) in the first and second periods, while it increased from 38 ha to 53 ha (39.4%) in the third period, reporting spatial tradeoff between the two land cover types. Meanwhile, urban areas in the outer zone increased from 10,729 ha to 15,112 ha (40%), from 15,112 ha to 21,377 ha (41.4%) and from 21,377 ha to 28,176 ha (31.8%) in the first, second and third periods, respectively, representing frontiers of suburbanization. On the other hand, the UGS in the outer zone decreased from 3624 ha to 3171 ha, from 3127 ha to 2555 ha and from 2555 ha to 1879 ha, with an annual rate of decline of 1.25%, 1.8% and 2.6%, respectively, showing increasing trend of UGS destruction for urban construction. Furthermore, the LEI analysis result showed that urban expansion pattern demonstrated largely an outlying growth characterized by differentiation and isolation of patches, whereas the infill and edge expansion pattern were insignificant and fluctuated over 30 years. Furthermore, the directional analysis showed that urban area predominately expanded in SEE,> SSE,> SSW,> SWW,> and NEE directions with varying magnitude in the first, second and third period, but decreased in third period in NWW, < NNW< and NNE directions. In response to such urban growth pattern, the center of gravity of urban area shifted from north to south during the study period, displaying main direction urbanization in recent years. Conclusively, zonal and directional studies are more effective in characterizing the Spatio-temporal dynamics variabilities of urban expansion and UGS change for informed urban planning towards sustainable urban development.

Tailoring photomorphogenic markers to organ growth dynamics

When a dark-germinated seedling reaches the soil surface and perceives sunlight for the first time, light signaling is activated to adapt the plant’s development and transition to autotrophism. During this process, functional chloroplasts assemble in the cotyledons and the seedling’s cell expansion pattern is rearranged to enhance light perception. Hypocotyl cells expand rapidly in the dark, while cotyledon cell expansion is suppressed. However, light reverses this pattern by activating cell expansion in cotyledons and repressing it in hypocotyls. The fact that light-regulated developmental responses, as well as the transcriptional mechanisms controlling them, are organ-specific has been largely overlooked in previous studies of seedling de-etiolation. To analyze the expansion pattern of the hypocotyl and cotyledons separately in a given Arabidopsis (Arabidopsis thaliana) seedling, we define an organ ratio, the morphogenic index (MI), which integrates either phenotypic or transcriptomic data for each tissue and provides an important resource for functional analyses. Moreover, based on this index, we identified organ-specific molecular markers to independently quantify cotyledon and hypocotyl growth dynamics in whole-seedling samples. The combination of these marker genes with those of other developmental processes occurring during de-etiolation will allow improved molecular dissection of photomorphogenesis. Along with organ growth markers, this MI contributes a key toolset to unveil and accurately characterize the molecular mechanisms controlling seedling growth.