Browse Articles

The differential impacts of team diversity as variability versus atypicality on team effectiveness

Early changes in microRNA expression in Arabidopsis plants infected with the fungal pathogen Fusarium graminearum

Plants respond to biotic stressors by modulating various processes in an attempt to limit the attack by a pathogen or herbivore. Triggering these different defense processes requires orchestration of a network of proteins and RNA molecules that includes microRNAs (miRNAs). These short RNA molecules (20–22 nucleotides) have been shown to be important players in the early responses of plants to stresses because they can rapidly regulate the expression levels of a network of downstream genes. The ascomycete Fusarium graminearum is an important fungal pathogen that causes significant losses in cereal crops worldwide. Using the well-characterized Fusarium-Arabidopsis pathosystem, we investigated how plants change expression of their miRNAs globally during the early stages of infection by F. graminearum. We have created a catalog of miRNAs that have differential expression in infected samples even before any visual symptoms of the infection are present. In addition to miRNAs that have been previously implicated in stress responses, we have also identified evolutionarily young miRNAs whose levels change significantly in response to fungal infection. Some of these young miRNAs have homologs present in cereals, which suggest that some of these miRNAs could be drivers of stress response. By examining if the miRNAs in this catalog have causal roles in plant infection response, a unique path toward development of plants with increased resistance to fungal pathogens can be developed.

Preclinical efficacy of CDK7 inhibitor–based combinations against myeloproliferative neoplasms transformed to AML

Abstract Rising blast percentage or secondary acute myeloid leukemia (sAML) transformation in myeloproliferative neoplasms (MPNs) leads to JAK1/2 inhibitor (JAKi) therapy resistance and poor survival. Here, we demonstrate that treatment with the CDK7 inhibitor (CDK7i) SY-5609 depletes phenotypically characterized post-MPN sAML stem/progenitor cells. In cultured post-MPN sAML SET2, HEL and patient-derived (PD) post-MPN sAML cells, SY-5609 treatment inhibited growth and induced lethality while sparing normal cells. RNA-sequencing analysis after SY-5609 treatment reduced mRNA expression of MYC, MYB, CDK4/6, PIM1, and CCND1 but increased expression of CDKN1A and BCL2L1. Mass spectrometry of SY-5609–treated MPN-sAML cells also reduced c-Myc, c-Myb, PIM1, and CDK4/6 but increased p21, caspase-9, and BAD protein levels. CRISPR-mediated CDK7 depletion also reduced cell viability of HEL cells. Cytometry by time of flight (CyTOF) analysis of SY-5609–treated PD post-MPN sAML stem/progenitor cells showed reduced c-Myc, CDK6, and PU.1 but increased protein levels of CD11b, p21, and cleaved caspase-3. Cotreatment with SY-5609 and ruxolitinib was synergistically lethal in HEL, SET2, and PD post-MPN sAML cells. A CRISPR screen in sAML cells revealed BRD4, CBP, and p300 as codependencies with CDK7i. Accordingly, cotreatment with SY-5609 and the bromodomain and extra-terminal protein inhibitor (BETi) OTX015 or pelabresib or the CBP/p300 inhibitor GNE-049 was synergistically lethal in MPN-sAML cells (including those exhibiting TP53 loss). Finally, in the HEL-Luc/GFP xenograft model, compared with each agent alone, cotreatment with SY-5609 and OTX015 reduced sAML burden and improved survival without host toxicity. These findings demonstrate promising preclinical activity of CDK7i-based combinations with BETi or CBP/p300 inhibitor against advanced MPNs, including post-MPN sAML.

Analysis of drought and extreme precipitation events in Thailand: trends, climate modeling, and implications for climate change adaptation

Microplastics block blood flow in the brain, mouse study reveals

Underwater paleontology inside cenotes reveals the Miocene-Pliocene fish diversity in the Yucatan Peninsula, southeast Mexico

The Yucatan Peninsula, southeast México, hosts a unique underwater karstic system of galleries connected by multiple sinkholes, locally called cenotes. This system is developed on a great Late Miocene to Early Pliocene carbonate platform belonging to the Carrillo Puerto Formation. The karstification process partially erodes these deposits’ surfaces and exposes the fossil assemblage. Here, we present the fossil fish diversity in underwater prospections in the Cenotes Sambulá, San Juan, and X-Nabuy. Our results indicate the presence of at least 11 different taxa, which include: 1) species that live today on Mexican coasts, such as Carcharhinus brachyurus, C. leucas, C. perezii, Carcharodon carcharias, and unidentified Rhinoptera species; 2) extinct taxa, such as †Galeocerdo mayumbensis, †Hemipristis serra, and †Otodus (Carcharocles) megalodon; 3) taxa that are not currently distributed in Mexican coasts, such as Carcharhinus macloti and representatives of the genus Aetomylaeus. Furthermore, a new Diodontidae species, †Chilomycterus dzonotensis sp. nov., is described. It represents an increment in the Neogene fish diversity in the Gulf of Mexico and supports a shallow marine environment associated with a coral reef system. The small size of some teeth indicates that the deposits of Carrillo Puerto could be a shelter for tiny marine organisms, and the presence of some taxa highlights local extinctions in the Western Atlantic during the Late Cenozoic.

The dark zone of CNS relapse in DLBCL

A transgenic mouse line with a 58 kb fragment deletion shows skeletal defects

Pre-siting of UAV stations for traffic accident assessment considering road dispersion

This paper investigates the issue of pre-site selection for drone stations with the aim of enhancing the rapid assessment capability of urban road traffic accidents. Firstly, the influence of traffic accidents on urban traffic is analyzed, and the potential application of drones in rapid response at the accident scene is explored. A minimization model is constructed with the goal of minimizing the cost of accident handling and reducing traffic congestion. To solve this problem, we improved the simulated annealing algorithm by combining the multi-neighborhood strategy, adaptive neighborhood size, and adding a taboo list, and verified the effectiveness of the algorithm. The validity of the model is tested through simulation examples, and the impact of the drone coverage radius and the distribution of accident points on the model performance is explored through sensitivity analysis, providing management insights for the pre-site selection of drone stations.

The hepcidin-ferroportin axis modulates liver endothelial cell BMP expression to influence iron homeostasis in mice

Abstract The liver hormone hepcidin regulates systemic iron homeostasis to provide enough iron for vital processes while limiting toxicity. Hepcidin acts by degrading its receptor ferroportin (encoded by Slc40a1) to decrease iron export to plasma. Iron controls hepcidin production in part by inducing liver endothelial cells (LECs) to produce bone morphogenetic proteins (BMPs) that activate hepcidin transcription in hepatocytes. Here, we used in vitro and in vivo models to investigate whether ferroportin contributes to LEC intracellular iron content to modulate BMP expression and, thereby, hepcidin. Quantitative proteomics of LECs from mice fed different iron diets demonstrated an inverse relationship between dietary iron and endothelial ferroportin expression. Slc40a1 knockdown primary mouse LECs and endothelial Slc40a1 knockout mice exhibited increased LEC iron and BMP ligand expression. Endothelial Slc40a1 knockout mice also exhibited altered systemic iron homeostasis with decreased serum and total liver iron but preserved erythropoiesis. Although endothelial Slc40a1 knockout mice had similar hepcidin expression to control mice, hepcidin levels were inappropriately high relative to iron levels. Moreover, when iron levels were equalized with iron treatment, hepcidin levels were higher in endothelial Slc40a1 knockout mice than in controls. Finally, LEC ferroportin levels were inversely correlated with hepcidin levels in multiple mouse models, and treatment of hepcidin-deficient mice with mini-hepcidin decreased LEC ferroportin expression. Overall, these data show that LEC ferroportin modulates LEC iron and consequently BMP expression to influence hepcidin production. Furthermore, LEC ferroportin expression is regulated by hepcidin, demonstrating a bidirectional communication between LECs and hepatocytes to orchestrate systemic iron homeostasis.

Ultrasound imaging of the perithyroid fascial space: a comparative analysis with anatomical correlations

Therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy in Sub-Saharan Africa: A scoping review

Introduction There are divergent views and limited data regarding therapeutic hypothermia (TH) for neonatal hypoxic ischaemic encephalopathy (HIE) in sub-Saharan Africa (SSA). Our aim was to map and synthesize the published literature describing the use of TH for HIE in SSA, and the associated outcomes. Method We searched Pubmed, Scopus, Google Scholar, and Web of Science from 1 January 1996 to 31 December 2023 for research studies, protocols, feasibility studies and surveys on term and near-term babies with HIE (population) treated with TH (concept) in SSA (context). Results Thirty records were included: Three surveys, one feasibility study and 26 publications describing 23 studies of 21 cohorts, cooling 1420 babies in South Africa, Uganda, and Ghana. There were five studies recruiting at follow-up, five pilot studies, one randomised controlled trial, one case series, and 10 birth cohorts. The methods and design of the studies were highly variable and often inadequate. Only three studies with adequately described and validated cooling methods, non-selective sequential recruitment, and neurological outcomes were identified. Two studies of babies from birth, both with intensive care facilities, reported survival with normal/mildly abnormal outcome in 71% at discharge in one study, and 71% at 12 months in another, with 16% cerebral palsy (CP) in survivors, and only 16% loss to follow-up. The third study, which only included clinic attenders after TH without intensive care, reported 7% CP in survivors, but 36% loss to follow-up. Conclusions Data from the adequately described TH studies in SSA indicate outcomes at discharge and twelve months which are similar to global norms. However, these data are limited to South Africa. Interpretation of other studies was limited by loss to follow-up, variable methodology and exclusion of babies with severe HIE in some studies. There is a need for standardised definitions to facilitate interpretation in TH studies.

BMPs and iron: the ins and outs

A hybrid differential evolution particle swarm optimization algorithm based on dynamic strategies

What went wrong at 23andMe? Why the genetic-data giant risks collapse

Bilateral internal iliac artery ligation in trauma patients with severe pelvic hemorrhage: A systematic review

Introduction Severe pelvic hemorrhage significantly contributes to mortality in trauma patients, yet the most effective treatment for severe pelvic injuries remains unclear. This systematic review evaluates the mortality and morbidity associated with bilateral internal iliac artery ligation (BIIAL) in patients experiencing severe hemorrhage from traumatic pelvic fractures. Methods Comprehensive searches were conducted in MEDLINE PubMed, EMBASE, and Cochrane databases until February 7, 2024, to identify relevant articles. The risk of bias in observational studies was assessed using the ROBINS-I tool, which evaluates bias risk in nonrandomized intervention studies. The primary outcome was mortality following BIIAL, with the secondary outcome being complications related to the procedure. Results The review included eight studies, all observational. The overall mortality rate after BIIAL ranged from 45.0% to 76.9%. Ischemic complications from BIIAL were infrequent. A high and unclear risk of bias due to confounding and participant selection was noted across the studies. Four studies highlighted distinct indications for BIIAL compared to angioembolization. BIIAL was employed for patients with severe hemodynamic instability or when angiography was not available. Conclusion Due to geographical limitations and significant heterogeneity among the studies reviewed, the true effect size of BIIAL remains indeterminate. Nevertheless, further prospective studies with robust designs are necessary. BIIAL holds potential as a viable option when angioembolization is not accessible or in cases of critical patient instability.

No exit: targeting RNA export in T-cell malignancy

Assessing the diagnostic accuracy of machine learning algorithms for identification of asthma in United States adults based on NHANES dataset

Correction: Human-machine interactions with clinical phrase prediction system, aligning with Zipf’s least effort principle?

CNS relapse in high-grade B-cell lymphoma with <i>MYC</i> and <i>BCL2</i> rearrangements and dark-zone signature–expressing DLBCL

Abstract High-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH-BCL2), or “double-hit lymphoma,” has been associated with a high risk of central nervous system (CNS) relapse. However, historic estimates are impacted by selection bias. We report CNS relapse rates associated with HGBCL-DH-BCL2 from a population-based cohort with complete fluorescence in situ hybridization testing, as well as diffuse large B-cell lymphoma morphology (DLBCL) tumors expressing the dark-zone gene expression signature (DZsig), which was originally derived from HGBCL-DH-BCL2. The 2-year CNS relapse risk in HGBCL-DH-BCL2 was 6.8%. CNS relapses were early, predominantly leptomeningeal (73%), and co-occurred with systemic relapse (64%). High-risk CNS International Prognostic Index (CNS-IPI) and concordant bone marrow involvement were associated with an elevated CNS relapse risk in HGBCL-DH-BCL2. The “refined cell-of-origin” classification assigned 20% of DLBCL morphology tumors with germinal center B-cell–like phenotype (GCB-DLBCL) into a distinct subgroup based on DZsig expression (DZsig+). CNS relapse risk in DZsig+ (2 year: 6.4%) was independent of HGBCL-DH-BCL2 status and was further stratified by the CNS-IPI. CNS relapse in DZsig-negative GCB-DLBCL was rare (2-year risk, 1.4%; P = .04 vs DZsig+) and exclusively parenchymal. Altogether, the CNS relapse risk in HGBCL-DH-BCL2 is lower than previously reported, and DZsig refines risk stratification in GCB-DLBCL.