Extensive Expansion Research Articles

Synergistic Effects of Type I PRMT1 and Type II PRMT5 Inhibitors Against Multiple Myeloma

Multiple myeloma (MM) is a plasma cell malignancy characterized by the extensive expansion of monoclonal aberrant plasma cells in the bone marrow and the second most prevalent hematological malignancies worldwide. Despite the promising outcomes of advanced therapies, relapsed/refractory (RR) diseases remain incurable, highlighting an unmet clinical need to identify novel therapeutic targets. An emerging field of investigation is the role of aberrant post-translational modifications in multiple myeloma pathology. Arginine methylation is one of the most predominant post-translational modifications in cells, catalyzed by protein arginine methyltransferases (PRMTs) that plays a crucial role in multiple cellular processes. Type I PRMTs catalyze mono- (MMA) and asymmetric demethylation (ADMA) of arginine; Type II PRMTs catalyze mono- and symmetric demethylation (SDMA) of arginine on proteins; Type III PRMT mediates MMA only. Aberrant expression of PRMTs is strongly associated with poor prognosis of solid cancers and hematologic malignancies. Recently, we identified PRMT1 as a novel therapeutic vulnerability in MM cells. Among PRMTs, PRMT1 is the highest expressed gene in MM cell lines and patient cells. The elevation of PRMT1 expression is strongly associated with relapsed/refractory patients and poor clinical outcomes. Deletion of PRMT1 and suppression of the PRMT1's enzymatic activity exhibited a strong anti-MM in vitro via suppressing cell cycle and elevating the apoptosis. We also found that inhibition of PRMT1 boosts the T cell activation in the co-culture setup, indicating a potential enhancement of immunotherapy. Using a subcutaneous xenograft model, we showed that suppressing PRTM1 in vivo by either genetic or pharmaceutical approaches robustly inhibits MM tumor growth and extends survival of tumor-bearing mice. Our findings demonstrated that PRMT1 is indispensable in MM. PRMT5, a PRMT type II, is prognostically relevant and a known druggable target in MM. PRMT1 and PRMT5 inversely regulate post-transcription and have been implicated in human cancers. Recent studies in solid tumor showed a strong anti-tumor effect in vivo using the combinational inhibition of PRMT1 and PRMT5. We hypothesize that PRMT1 and PRMT5 might have a complementary function in MM cells. The combinational inhibition PRMT1 and PRTM5 will exhibit a synergistic anti-MM effect. To address this hypothesis, we treated MM cell lines with two clinical trial inhibitors: GSK3368715 (GSK) and EPZ 015666 (EPZ), suppressing PRMT type I and type II inhibitor, respectively. We first performed dose-dependent cell viability inhibition and selected effective doses for drug combination treatments in three different MM cell lines. The combination of GSK and EPZ demonstrated a strong synergistic effect in suppressing the viability of MM cells. Using the SynergyFinder algorithm, we found that the synergistic indexes (>10, synergism) for 3 MM cell lines JJN3, MM1S, and KMS11 were 33.5, 32.8, and 14.3, respectively. We next assessed the effects of combined treatment on the cell cycle and apoptosis of MM cells. We found that combination of GSK and EPZ strikingly elevated the apoptosis and suppressed cell cycle of MM cell lines compared single treatment and untreated control. Intriguingly, the combination treatment of two inhibitors significantly decreased MMA, SDMA, and ADMA, suggesting a robust suppression of global arginine methylation. Of note, we found a similar anti-MM effect when treating bortezomib-resistant MM cells with GSK and EPZ, indicating that PRMT type I and type II inhibitors potentially have a substantial clinical impact on relapsed MM. Of note, the same dose of GSK and EPZ that exhibits the synergistic anti-MM effect, didn't suppress the viability of healthy peripheral blood cells. In summary, our preliminary data suggest that suppression of both PRMT type I and type II might provide a potential effective combination treatment for both newly diagnosed and relapsed MM patients. We're currently investigating the underling mechanisms of how PRMTs regulate MM pathology and validating the in vivo efficacy of combination treatment using patient-derived xenograft.

Stability Analysis and Environmental Influence Evaluation on a Hybrid Mooring System for a Floating Offshore Wind Turbine

Floating offshore wind turbines (FOWTs) are one of the innovative solutions to achieve net-zero emissions. Given that Taiwan has abundant wind power resources in its western waters and wind farms are evaluated as potential sites, a strategic emphasis on the extensive expansion of wind power is imperative. This paper chooses four different designs of hybrid mooring systems, comparing them with the conventional pure chain mooring arrangement in shallow water regions in Taiwan through integrated numerical simulations, ANSYS AQWA, and Orcina OrcaFlex. The use of synthetic fiber ropes in hybrid moorings provides substantial economic and operational advantages, making them the preferred alternative to traditional chains in deepwater offshore renewable energy (ORE) mooring configurations. Hybrid mooring enables the FOWT to survive in extreme sea conditions and is presented as the ultimate limit state (ULS) and fatigue limit state (FLS). In addition, hybrid mooring not only reduces mooring line costs but also minimizes the footprint area on the seabed, enhancing economic competitiveness and optimizing marine space utilization. However, it increases the entanglement risk that may pose a potential threat to marine mammals. Building on prior research, this paper proposes a unique approach to calculate the mooring line swept volume, which is essential for entanglement assessment and marine spatial planning.

Impacts of long-term organic manure inputs on cultivated soils with various degradation degrees

With an increasing concern of soil health and sustainable development, organic manure application has been readdressed in recent years. In Northeast China, the agricultural industry is highly developed and organic manure resources are abundant, but soil degradation is serious due to extensive expansion of cultivation. Currently, limited information is available on how soils with various degradation degrees respond to long-term manure fertilization. Given that, a comparative study was conducted based on soil functional assessment of croplands with over 35 years of manure fertilization (maize straw compost, SA; cattle manure, CA) and various degradation degrees (none, light, moderate, and heavy). Soils in these croplands were loess-derived Mollisols and concentrated on a gentle to flat slope. Except for the difference in manure fertilization (SA and CA), similar field managements were adopted for these croplands during the past 35 years. Results showed that the impacts of erosion degradation and manure fertilization on soil physical structure lasted across the whole profile (0 ∼ 120 cm), while their impacts on soil nutrient properties were concentrated in shallow layers (<50 cm). Meanwhile, erosion degradation dominated 17.9% of the variance of soil physical structure, and soil profile depth contributed to 15.9% of soil nutrient variation. According to field validation regarding soil erosion modulus and crop yield, principal component analysis (PCA) with a nonlinear scoring method showed a good performance on the integrated soil functional index (ISI) assessment in this study area. The ISI of these croplands was found to be minimally characterized by BD, SOC, TN, AK, sand content, and CEC (R2 >0.64, p < 0.001). In addition, manure fertilization could significantly improve the ISI and maize yield for degraded soils, but had a slight impact on these two indicators for non-degraded soils. In terms of contribution to ISI improvement, SA (1.79% ∼ 283.73%) generally outperformed CA (4.53% ∼ 212.83%), while the latter was more effective in altering soil structure in deep layers (>70 cm). Generally, the ISI and maize yield were more susceptible to erosion degradation than manure fertilization. The obtained results provide useful information for a better cropland management in Northeast China.

A palisade-shaped membrane reservoir is required for rapid ring cell inflation in Drechslerella dactyloides

Fusion of individual vesicles carrying membrane-building materials with the plasma membrane (PM) enables gradual cell expansion and shape change. Constricting ring (CR) cells of carnivorous fungi triple in size within 0.1-1 s to capture passing nematodes. Here, we investigated how a carnivorous fungus, Drechslerella dactyloides, executes rapid and irreversible PM expansion during CR inflation. During CR maturation, vesicles carrying membrane-building materials accumulate and fuse, forming a structure named the Palisade-shaped Membrane-building Structure (PMS) around the rumen side of ring cells. After CR inflation, the PMS disappears, with partially inflated cells displaying wavy PM and fully inflated cells exhibiting smooth PM, suggesting that the PMS serves as the reservoir for membrane-building materials to enable rapid and extensive PM expansion. The DdSnc1, a v-SNARE protein, accumulates at the inner side of ring cells and is necessary for PMS formation and CR inflation. This study elucidates the unique cellular mechanisms underpinning rapid CR inflation.

Integrated evaluation and attribution of urban flood risk mitigation capacity: A case of Zhengzhou, China

Study regionThe Zhengzhou City in China Study focusUrban flood risk mitigation (UFRM) refers to the runoff retention capacity of land surface in urban regions. Previous studies have focused on assessing the UFRM change in central urban areas. Nevertheless, analysis of the UFRM change considering the heterogeneity of urban and rural gradient is scarce. This study aims to evaluate the spatiotemporal change of UFRM and its influencing factors in different urban functional zones. An integrated framework combining the hydrological model and geographic information system (GIS) has been established to assess the evolution of UFRM in Zhengzhou between 2000 and 2020. New hydrological insights for the regionThe findings illustrate the following: (1) The UFRM of Zhengzhou experienced a 10.76% increase from 2000 to 2010, followed by a subsequent 3.38% decrease from 2010 to 2020.(2) UFRM increased in ecological areas while decreasing in urban regions, revealing a disparity between UFRM supply and demand. (3) The adverse impact of impervious surfaces on UFRM surpasses the influence of precipitation intensity in urban regions. As a result, this study suggests that urban areas should avoid extensive expansion of impervious surfaces and prioritize implementing low-impact development practices. The ecological zones should implement rigorous policies to protect natural preservation. These findings provide policymakers a scientific foundation for devising sustainable urban development strategies to enhance urban flood resilience.

Bayesian areal disaggregation regression to predict wildlife distribution and relative density with low-resolution data.

For species of conservation concern and human-wildlife conflict, it is imperative that spatial population data be available to design adaptive-management strategies and be prepared to meet challenges such as land use and climate change, disease outbreaks, and invasive species spread. This can be difficult, perhaps impossible, if spatially explicit wildlife data are not available. Low-resolution areal counts, however, are common in wildlife monitoring, that is, the number of animals reported for a region, usually corresponding to administrative subdivisions, for example, region, province, county, departments, or cantons. Bayesian areal disaggregation regression is a solution to exploit areal counts and provide conservation biologists with high-resolution species distribution predictive models. This method originated in epidemiology but lacks experimentation in ecology. It provides a plethora of applications to change the way we collect and analyze data for wildlife populations. Based on high-resolution environmental rasters, the disaggregation method disaggregates the number of individuals observed in a region and distributes them at the pixel level (e.g., 5 × 5 km or finer resolution), thereby converting low-resolution data into a high-resolution distribution and indices of relative density. In our demonstrative study, we disaggregated areal count data from hunting bag returns to disentangle the changing distribution and population dynamics of three deer species (red, sika, and fallow) in Ireland from 2000 to 2018. We show an application of the Bayesian areal disaggregation regression method and document marked increases in relative population density and extensive range expansion for each of the three deer species across Ireland. We challenged our disaggregated model predictions by correlating them with independent deer surveys carried out in field sites and alternative deer distribution models built using presence-only and presence-absence data. Finding a high correlation with both independent data sets, we highlighted the ability of Bayesian areal disaggregation regression to accurately capture fine-scale spatial patterns of animal distribution. This study uncovers new scenarios for wildlife managers and conservation biologists to reliably use regional count data disregarded so far in species distribution modeling. Thus, it represents a step forward in our ability to monitor wildlife population and meet challenges in our changing world.

Accessing childcare: Parents’ logistical challenges and gender equality

Accessing childcare: Parents’ logistical challenges and gender equality Prof Ingela Naumann from the University of Fribourg, explains why reducing parents’ logistical challenges in coordinating work and childcare matters for gender equality. Over the last two decades, we have seen an extensive expansion of early childhood education and care (ECEC) services across the countries of the OECD. A novel and ground-breaking consensus amongst policymakers and society had emerged by the beginning of the 21st century that ECEC is an essential pillar of our knowledge-based economies (see, e.g. European Commission 2018): they benefit children by fostering good child development – if the provided services are of good quality – thus supporting positive life courses and productivity of future generations; they help parents to remain active in the labour market, thus contributing to the prevention of family/child poverty and, again, boosting productivity.

Cardiomyocyte precursors generated by direct reprogramming and molecular beacon selection attenuate ventricular remodeling after experimental myocardial infarction

BackgroundDirect cardiac reprogramming is currently being investigated for the generation of cells with a true cardiomyocyte (CM) phenotype. Based on the original approach of cardiac transcription factor-induced reprogramming of fibroblasts into CM-like cells, various modifications of that strategy have been developed. However, they uniformly suffer from poor reprogramming efficacy and a lack of translational tools for target cell expansion and purification. Therefore, our group has developed a unique approach to generate proliferative cells with a pre-CM phenotype that can be expanded in vitro to yield substantial cell doses.MethodsCardiac fibroblasts were reprogrammed toward CM fate using lentiviral transduction of cardiac transcriptions factors (GATA4, MEF2C, TBX5, and MYOCD). The resulting cellular phenotype was analyzed by RNA sequencing and immunocytology. Live target cells were purified based on intracellular CM marker expression using molecular beacon technology and fluorescence-activated cell sorting. CM commitment was assessed using 5-azacytidine-based differentiation assays and the therapeutic effect was evaluated in a mouse model of acute myocardial infarction using echocardiography and histology. The cellular secretome was analyzed using mass spectrometry.ResultsWe found that proliferative CM precursor-like cells were part of the phenotype spectrum arising during direct reprogramming of fibroblasts toward CMs. These induced CM precursors (iCMPs) expressed CPC- and CM-specific proteins and were selectable via hairpin-shaped oligonucleotide hybridization probes targeting Myh6/7-mRNA–expressing cells. After purification, iCMPs were capable of extensive expansion, with preserved phenotype when under ascorbic acid supplementation, and gave rise to CM-like cells with organized sarcomeres in differentiation assays. When transplanted into infarcted mouse hearts, iCMPs prevented CM loss, attenuated fibrotic scarring, and preserved ventricular function, which can in part be attributed to their substantial secretion of factors with documented beneficial effect on cardiac repair.ConclusionsFibroblast reprogramming combined with molecular beacon-based cell selection yields an iCMP-like cell population with cardioprotective potential. Further studies are needed to elucidate mechanism-of-action and translational potential.Graphical

Forestry feedbacks in Malezales’ degradation: Insights from past to plan future policy-driven forestry expansion over wetlands in Argentina

The degradation of wetlands is a worrying phenomenon, given its ecosystemic importance due to the provision of environmental services. In Argentina, the process of wetland degradation is fast and almost unknown due to the lack of control and monitoring. Malezales grasslands are wetland ecosystems, indeed poorly studied and endemic of Argentina's northeast. This study aimed to understand the impacts of policy-driven forestry expansion in wetlands, searching for tools and patterns to plan sustainable afforestation. Geographic information systems and remote sensing-based models were used to produce and analyze historical data of the forestry expansion and malezales degradation on inceptsols located in northeastern Corrientes, Argentina. The results showed that the region experienced extensive forestry expansion over the last 20 years. Pinus spp. plantations expanded on the most degraded malezales, which suggests some sustainability in the expansion process. However, the remaining malezales present current worrying levels of degradation. The intensification of the degradation process is imminent because livestock pressure on malezales has been intensified after the loss of areas due to the forestry increasing. We present a preliminary zoning of areas for conservation or forestry expansion in malezales. We found that 40.2% (47571 ha) of the current area of malezales could be used for forestry expansion, while 59.81% (about 70793 ha, 41.56% of the original ecosystem) is of priority for conservation or protection actions. A complete zoning of malezales is recommended, and policies to foment the correct management of malezales and forestry should therefore be implemented.

Intestinal-specific Hdac3 deletion increases susceptibility to colitis and small intestinal tumour development in mice fed a high fat diet.

High fat diets, and inflammation are risk factors for colon cancer, however the underlying mechanisms remain to be fully elucidated. The transcriptional co-repressor HDAC3 has recently emerged as a key regulator of intestinal epithelial responses to diet and inflammation with intestinal-specific Hdac3 deletion (Hdac3IKO) in mice increasing lipid oxidation genes and the rate of lipid oxidation in enterocytes. Hdac3IKO mice are also predisposed to experimentally induced colitis, however whether this is driven by the intestinal metabolic reprogramming, and whether this predisposes these mice to intestinal tumourigenesis is unknown. Herein, we examined the effects of intestinal-specific Hdac3 deletion on colitis-associated intestinal tumourigenesis in mice fed a standard (STD) or HF diet (HFD). Hdac3IKO mice were highly prone to experimentally induced colitis, which was further enhanced by a HFD. Hdac3deletion also accelerated intestinal tumour development, specifically when fed a HFD and most notably in the small intestine where lipid absorption is maximal. Expression of proteins involved in fatty acid metabolism and oxidation (SCD1, EHHADH) were elevated in the small intestine of Hdac3IKO mice fed a HFD, and these mice displayed increased levels of lipid peroxidation, DNA damage, and apoptosis in their villi, as well as extensive expansion of the stem cell and progenitor cell compartment. These findings reveal a novel role for Hdac3 in suppressing colitis and intestinal tumorigenesis, particularly in the context of consumption of a HFD, and reveal a potential mechanism by which HFDs may increase intestinal tumorigenesis by increasing lipid oxidation, DNA damage and intestinal epithelial cell turnover.

Urban density and socioeconomic characteristics of informal settlements: evidence of interrelation from Maputo, Mozambique

Several studies have documented extensive low-density urban expansion of cities in sub-Saharan Africa, exacerbating issues of inadequate infrastructure, limited mobility and human impact on the environment. However, the relation between socioeconomic factors and urban expansion trends in sub-Saharan Africa remains understudied. This study investigates the links between household socioeconomic status and urban form of informal settlements based on case studies in Maputo, Mozambique. The findings of the study underscore that (1) built densification occurs over time, reflecting an incremental house expansion process enabled by household economic resources; (2) households with higher socioeconomic status consume comparatively more land, contributing to urban expansion; (3) households in more recently established settlements within the city limits have higher socioeconomic status than households in older settlements located in comparable proximity to the city centre; and (4) rental housing is more widespread in the centrally located settlements and accommodates younger residents with lower socioeconomic status.

Massive multi-player multi-armed bandits for IoT networks: An application on LoRa networks

More and more manufacturers, as part of the transition towards Industry 4.0, are using Internet of Things (IoT) networks for more efficient production. The wide and extensive expansion of IoT devices and the variety of applications generate different challenges, mainly in terms of reliability and energy efficiency. In this paper, we propose an approach to optimize the performance of IoT networks by making the IoT devices intelligent using machine learning techniques. We formulate the optimization problem as a massive multi-player multi-armed bandit and introduce two novel policies: Decreasing-Order-Reward-Greedy (DORG) focuses on the number of successful transmissions, while Decreasing-Order-Fair-Greedy (DOFG) also guarantees some measure of fairness between the devices. We then present an efficient way to manage the trade-off between transmission energy consumption and packet losses in Long-Range (LoRa) networks using our algorithms, by which LoRa nodes adjust their emission parameters (Spreading Factor and transmitting power). We implement our algorithms on a LoRa network simulator and show that such learning techniques largely outperform the Adaptive Data Rate (ADR) algorithm currently implemented in LoRa devices, in terms of both energy consumption and packet losses.

Local flow control by phononic subsurfaces over extended spatial domains

Local phonon motion underneath a surface interacting with a flow may cause the flow to passively stabilize, or destabilize, as desired within the region adjacent to the subsurface motion. This mechanism has been extensively analyzed over only a spatial region on the order of the instability wavelength along the fluid–structure interface. Here, we uncover fundamental relations between the behavior of flow instabilities and the frequency response characteristics of the phononic subsurface structure admitting the elastic motion. These relations are then utilized to demonstrate the possibility of extensive spatial expansion of the control regime along the downstream direction with minimal loss of performance—potentially covering the entire surface exposed to the flow.

Birthweight of the subsequent singleton pregnancy following a first twin or singleton pregnancy.

Birthweight is an important pregnancy indicator strongly associated with infant, child, and later adult life health. Previous studies have found that second-born babies are, on average, heavier than first-born babies, indicating an independent effect of parity on birthweight. Existing data are mostly based on singleton pregnancies and do not consider higher order pregnancies. We aimed to compare birthweight in singleton pregnancies following a first twin pregnancy relative to a first singleton pregnancy. This was a prospective registry-based cohort study using maternally linked offspring with first and subsequent pregnancies registered in the Medical Birth Registry of Norway between 1967 and 2020. We studied offspring birthweights of 778 975 women, of which 4849 had twins and 774 126 had singletons in their first pregnancy. Associations between twin or singleton status of the first pregnancy and birthweight (grams) in subsequent singleton pregnancies were evaluated by linear regression adjusted for maternal age at first delivery, year of first pregnancy, maternal education, and country of birth. We used plots to visualize the distribution of birthweight in the first and subsequent pregnancies. Mean combined birthweight of first-born twins was more than 1000 g larger than mean birthweight of first-born singletons. When comparing mean birthweight of a subsequent singleton baby following first-born twins with those following first-born singletons, the adjusted difference was just 21 g (95% confidence interval 5-37 g). Birthweights of the subsequent singleton baby were similar for women with a first twin or a first singleton pregnancy. Although first twin pregnancies contribute a greater combined total offspring birthweight including more extensive uterine expansion, this does not explain the general parity effect seen in birthweight. The physiological reasons for increased birthweight with parity remain to be established.

Absence of Lugol staining indicates initiation of esophageal squamous cell carcinoma: A combined genomic and epidemiologic study

The genomic characteristics during the carcinogenic process of esophageal squamous cell carcinoma (ESCC) remain largely unknown. We report here the genomic characteristics of 106 esophageal tissues of various stages from a population-based screening cohort in China ("Endoscopic Screening for Esophageal Cancer in China" trial) and 57 ESCC tissues from a local hospital. A significant increase in somatic mutation and copy number alterations is observed in the non-dysplastic Lugol unstaining lesions (ND-LULs). Extensive clonal expansion has emerged in the ND-LULs to an extent similar to that in higher-stage lesions. The burden of genomic alterations correlates with the size of LULs in the ND-LULs. 8-year follow-up shows that ND-LULs harbor an increased risk of progression to ESCC (adjusted IRR6-10mm vs. none= 4.66, adjusted IRR>10mm vs. none= 40.70), and the risk is correlated with LUL size for both non-dysplastic and dysplastic lesions. Lugol unstaining can be the initial stage in the carcinogenic process of ESCC.

On the effect of the poisson’s ratio on samples subjected to shearing

The effect of shearing on finite-sized auxetic and non-auxetic samples was examined through finite element simulations. It was shown that when shear was applied in a manner representative of a common shear-testing setup, which is not dissimilar to the situation encountered in sports applications, auxetics manifested very different characteristics compared to their non-auxetic counterparts; with very pronounced edge effects. These included extensive lateral expansion of the samples and the formation of non-insignificant concave creases on their exposed lateral faces. It was shown that these creases became even more pronounced when the samples were subjected to combined shear and compressive loads and need to be taken into consideration when assessing the suitability, or otherwise, of auxetics for practical applications where shear loading may be present to a certain extent.

Hydrochemical Characterization and Water Quality Assessment for Drinking and Irrigation Purposes Using WQI and GIS Techniques in the Upper Omo River Basin, Southern Ethiopia

Groundwater is an important source of drinking water and irrigation in Ethiopia’s present study area of the upper Omo River catchment. The present study area has an increasing demand for high-quality groundwater. Extensive irrigation and urban expansion are ongoing in the study area, seriously compromising groundwater quality. A study was conducted in Ethiopia’s upper Omo River catchment to assess groundwater’s suitability for drinking water and agricultural purposes. In total, 58 water samples were collected for this study. Based on the WHO and Ethiopian standards for assessing water quality, the study’s results have been analyzed and compared. The groundwater’s primary ion and physicochemical properties were plotted using GIS technology. Based on the results of the hydrochemical analysis, three water quality index (WQI) zones were identified: excellent (58.82%), good (35.29%), and poor (5.88%). From the Piper diagram plots, five different types of water were identified as Ca-HCO3, Na-HCO3, mixed Ca-Na-HCO3, NaCl, and CaCl, out of the total of fifty-eight samples collected from the study area. The present study found that in the area, most water samples are suitable for drinking, except for a few parameters above the standards for drinking water set by the World Health Organization and Ethiopian drinking water quality standards. Except for the three samples, EC, SAR, and PI data indicate that most of the area’s water samples are suitable for irrigation. Water quality indices, irrigation water quality methods, and GIS techniques are crucial for assessing water quality based on the study.

Urban expansion, subnormal agglomerations and provision of sanitation services: a case study of the Metropolitan Region of Belém

The process of urban growth in Brazil remains accelerated and presents a wide variety of realities. In this article, we aim to analyze the urban expansion in the Metropolitan Region of Belém (RMB), verifying whether it occurred intensively or extensively, and whether this expansion was accompanied by an increase in subnormal agglomerations and the provision of sanitation services. The methodology was based on the elaboration of land use and occupation maps in the urban area of the RMB and on obtaining data referring to subnormal agglomerations and the scope of basic sanitation services, made available by the Brazilian Institute of Geography and Statistics. The results showed that the RMB had more extensive urban expansion in the 1990s, with a smaller expansion between 1999 and 2017. However, the coverage of basic sanitation services did not follow this expansion process and in the spaces inserted by the expansion process subnormal clusters were concentrated.

Nanotechnology in Agriculture: Feeding the Future a Brief Review by Leonard Copping

The world faces a challenge. The global population is increasing while climate change is applying stress to traditional farming. As a result food security and sustainable agriculture is facing a challenge the likes of which it has never faced before. Failure to address it could result in catastrophe. But developments in nanotechnology could be about to help ease the impending crisis. Developments could see it improve crop yields without resorting to extensive land expansion or excessive use of agrochemicals as well as enabling more efficient resource management. If it delivers, the rewards could be significant for investors and mankind alike. According to a report by Insight Analytic, the global agricultural nanotechnology market size was valued at some $321.1 billion in 2022. It is predicted to reach $868.98 billion by 2031 with a CAGR of 11.94%. The report said: “The development of the global market will be fuelled by the merger of improved agricultural techniques with nanotechnologies over the next five years. Additionally, the benefits can lower threats, including air and ground pollution, soil acidification, eutrophication, declining soil fertility and biodiversity loss. With the global population’s growth, rising demand for crops with higher yields will further support the expansion of the industry.

Minichromosome maintenance protein 10 (mcm10) regulates hematopoietic stem cell emergence in the zebrafish embryo.

Hematopoietic stem cells (HSCs) guarantee the continuous supply of all blood lineages during life. In response to stress, HSCs are capable of extensive proliferative expansion, whereas in steady state, HSCs largely remain in a quiescent state to prevent their exhaustion. DNA replication is a very complex process, where many factors need to exert their functions in a perfectly concerted manner. Mini-chromosome-maintenance protein 10 (Mcm10) is an important replication factor, required for proper assembly of the eukaryotic replication fork. In this report, we use zebrafish to study the role of mcm10 during embryonic development, and we show that mcm10 specifically regulates HSC emergence from the hemogenic endothelium. We demonstrate that mcm10-deficient embryos present an accumulation of DNA damages in nascent HSCs, inducing their apoptosis. This phenotype can be rescued by knocking down p53. Taken all together, our results show that mcm10 plays an important role in the emergence of definitive hematopoiesis.