Browse Articles

Structural basis of Spliced Leader RNA recognition by the Trypanosoma brucei cap-binding complex

Abstract Kinetoplastids are a clade of eukaryotic protozoans that include human parasitic pathogens like trypanosomes and Leishmania species. In these organisms, protein-coding genes are transcribed as polycistronic pre-mRNAs, which need to be processed by the coupled action of trans-splicing and polyadenylation to yield monogenic mature mRNAs. During trans-splicing, a universal RNA sequence, the spliced leader RNA (SL RNA) mini-exon, is added to the 5’-end of each mRNA. The 5’-end of this mini-exon carries a hypermethylated cap structure and is bound by a trypanosomatid-specific cap-binding complex (CBC). The function of three of the kinetoplastid CBC subunits is unknown, but an essential role in cap-binding and trans-splicing has been suggested. Here, we report cryo-EM structures that reveal the molecular architecture of the Trypanosoma brucei CBC (TbCBC) complex. We find that TbCBC interacts with two distinct features of the SL RNA. The TbCBP20 subunit interacts with the m7G cap while TbCBP66 recognizes double-stranded portions of the SL RNA. Our findings pave the way for future research on mRNA maturation in kinetoplastids. Moreover, the observed structural similarities and differences between TbCBC and the mammalian cap-binding complex will be crucial for considering the potential of TbCBC as a target for anti-trypanosomatid drug development.

Erratum: Grotzinger et al., “Diurnal Fluctuations in Steroid Hormones Tied to Variation in Intrinsic Functional Connectivity in a Densely Sampled Male”

Anomaly detection in multidimensional time series for water injection pump operations based on LSTMA-AE and mechanism constraints

Single-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis

Abstract A balanced activity of cGMP signaling contributes to the maintenance of cardiovascular homeostasis. Vascular smooth muscle cells (VSMCs) can generate cGMP via three ligand-activated guanylyl cyclases, the NO-sensitive guanylyl cyclase, the atrial natriuretic peptide (ANP)-activated GC-A, and the C-type natriuretic peptide (CNP)-stimulated GC-B. Here, we study natriuretic peptide signaling in murine VSMCs and atherosclerotic lesions. Correlative profiling of pathway activity and VSMC phenotype at the single-cell level shows that phenotypic modulation of contractile VSMCs to chondrocyte-like plaque cells during atherogenesis is associated with a switch from ANP/GC‑A to CNP/GC‑B signaling. Silencing of the CNP/GC-B axis in VSMCs results in an increase of chondrocyte-like plaque cells. These findings indicate that the CNP/GC-B/cGMP pathway is a marker and atheroprotective regulator of modulated VSMCs, limiting their transition to chondrocyte-like cells. Overall, this study highlights the plasticity of cGMP signaling in VSMCs and suggests analogies between CNP-dependent remodeling of bone and blood vessels.

Efficient pressure regulation in nonlinear shell-and-tube steam condensers via a Novel TDn(1 + PIDn) controller and DCSA algorithm

Author Correction: ChromaFold predicts the 3D contact map from single-cell chromatin accessibility

Erratum: Buttini et al., “Expression of Human Apolipoprotein E3 or E4 in the Brains of<i>Apoe^−/−</i>Mice: Isoform-Specific Effects on Neurodegeneration”

A functional integral approach to magnon mediated plasmon friction

Understanding the spread of agriculture in the Western Mediterranean (6th-3rd millennia BC) with Machine Learning tools

Abstract The first Neolithic farmers arrived in the Western Mediterranean area from the East. They established settlements in coastal areas and over time migrated to new environments, adapting to changing ecological and climatic conditions. While farming practices and settlements in the Western Mediterranean differ greatly from those known in the Eastern Mediterranean and central Europe, the extent to which these differences are connected to the local environment and climate is unclear. Here, we tackle this question by compiling data and proxies at a superregional and multi-scale level, including archaeobotanical information, radiocarbon dates and paleoclimatic models, then applying a machine learning approach to investigate the impact of ecological and climatic constraints on the first Neolithic humans and crops. This approach facilitates calculating the pace of spread of farming in the Western Mediterranean area, modelling and estimating the potential areas suitable for settlement location, and discriminating distinct types of crop cultivation under changing climatic conditions that characterized the period 5900 – 2300 cal. BC. The results of this study shed light onto the past climate variability and its influence on human distribution in the Western Mediterranean area, but also discriminate sensitive parameters for successful agricultural practices.

Impact of aspirin on biochemical recurrence of prostate cancer after robot assisted radical prostatectomy in a multicenter retrospective cohort study

Neuronal segmentation in cephalopod arms

MRI-guided focused ultrasound for treating Parkinson’s disease with human mesenchymal stem cells

Author Correction: Allostery can convert binding free energies into concerted domain motions in enzymes

Improving the thermal performance of PVC windows with pultruded thermoplastic reinforcement

CPK1 activates CNGCs through phosphorylation for Ca2+ signaling to promote root hair growth in Arabidopsis

Abstract Cyclic nucleotide-gated channel 5 (CNGC5), CNGC6, and CNGC9 (CNGC5/6/9 for simplicity) control Arabidopsis root hair (RH) growth by mediating the influx of external Ca2+ to establish and maintain a sharp cytosolic Ca2+ gradient at RH tips. However, the underlying mechanisms for the regulation of CNGCs remain unknown. We report here that calcium dependent protein kinase 1 (CPK1) directly activates CNGC5/6/9 to promote Arabidopsis RH growth. The loss-of-function mutants cpk1-1, cpk1-2, cngc5-1 cngc6-2 cngc9-1 (shrh1/short root hair 1), and cpk1 shrh1 show similar RH phenotypes, including shorter RHs, more RH branching, and dramatically attenuated cytosolic Ca2+ gradients at RH tips. The main CPK1-target sites are identified as Ser20, Ser27, and Ser26 for CNGC5/6/9, respectively, and the corresponding alanine substitution mutants fail to rescue RH growth in shrh1 and cpk1-1, while phospho-mimic versions restore the cytosolic Ca2+ gradient at RH apex and rescue the RH phenotypes in the same Arabidopsis mutants. Thus we discover the CPK1-CNGC modules essential for the Ca2+ signaling regulation and RH growth in Arabidopsis.

Erratum: Neupane et al., “Role of the STING→IRF3 Pathway in Ambient GABA Homeostasis and Cognitive Function”

The effect of cervical length on procedure time and VAS pain score in office hysteroscopy

Microglial NLRP3-gasdermin D activation impairs blood-brain barrier integrity through interleukin-1β-independent neutrophil chemotaxis upon peripheral inflammation in mice

Eight weeks of aerobic exercise, but not four, improves insulin sensitivity and cardiovascular performance in young women

Abstract Regular aerobic exercise has a significant impact on glucose metabolism and lipid profiles, contributing to overall health improvement. However, evidence for optimal exercise duration to achieve these effects is limited. This study aims to explore the effects of 4 and 8 weeks of moderate-intensity aerobic exercise on glucose metabolism, lipid profiles, and associated metabolic changes in young female students with insulin resistance and varying body mass, seeking to determine the optimal duration for physiological adaptations. Twenty-eight physically semi-active female students were randomly assigned to 4-week (G4, n = 13, age = 23.31 ± 5.19, BMI = 24.78 ± 5.87) and 8-week (G8, n = 15, age = 21.8 ± 2.56, BMI = 24.95 ± 4.81) training groups. The aerobic intervention maintained an intensity of 40–70% of maximum heart rate (HRmax). 6-min-walk test (6MWT), handgrip strength tests, insulin, HOMA-IR, lipid profiles, and metabolic profiles were assessed pre- and post-intervention. Following the intervention, G8, but not G4, exhibited a significant decrease in HOMA-IR (-14.59%, p = 0.047). The improvement in HOMA-IR was accompanied by notable improvements in 6-MWT (+ 38.18%, p &lt; 0.001) and handgrip strength (+ 11.62, p = 0.027 and + 17.59%, p = 0.013), and increased levels of bilirubin degradation products, ribose, and glutarate. The elevated levels of bilirubin degradation products, known for their antioxidant properties, suggested a potential antioxidative response triggered by prolonged aerobic exercise. Additionally, an increase in ribose and glutarate indicated improved metabolic flexibility and enhanced utilization of alternative energy substrates. The 8-week aerobic exercise regimen demonstrated enhanced insulin sensitivity, upper body strength, and cardiovascular performance in young females compared to a 4-week regimen by triggering specific metabolic adaptations. These findings emphasize the complex relationship between exercise duration, metabolic adaptations, and overall well-being in young women, providing valuable insights for optimizing exercise prescriptions in promoting metabolic health.

Long-term memory plasticity in a decade-long connectivity study post anterior temporal lobe resection

Abstract Approximately 40% of individuals undergoing anterior temporal lobe resection for temporal lobe epilepsy experience episodic memory decline. There has been a focus on early memory network changes; longer-term plasticity and its impact on memory function are unclear. Our study investigates neural mechanisms of memory recovery and network plasticity over nearly a decade post-surgery. We assess memory network changes, from 3–12 months to 10 years postoperatively, in 25 patients (12 left-sided resections) relative to 10 healthy matched controls, using longitudinal task-based functional MRI and standard neuropsychology assessments. We observe key adaptive changes in memory networks of a predominantly seizure-free cohort. Ongoing neuroplasticity in posterior medial temporal regions and contralesional cingulum or pallidum contribute to long-term verbal and visual memory recovery. Here, we show the potential for sustained cognitive improvement and importance of strategic approaches in epilepsy treatment, advocating for conservative surgeries and long-term use of cognitive rehabilitation for ongoing recovery.