The oncogenic lncRNA MIR503HG suppresses cellular senescence counteracting supraphysiological androgen treatment in prostate cancer.

Background: The androgen receptor (AR), a ligand-dependent transcription factor, plays a key role in regulating prostate cancer (PCa) growth. The novel bipolar androgen therapy (BAT) uses supraphysiological androgen levels (SAL) that suppresses growth of PCa cells and induces cellular senescence functioning as a tumor suppressive mechanism. The role of long non-coding RNAs (lncRNAs) in the regulation of SAL-mediated senescence remains unclear.

Functional circuits of LYL1 controlled by supraphysiological androgen in prostate cancer cells to regulate cell senescence.

Background: Prostate cancer (PCa) is a public health problem mostly reported in developed countries. The androgen receptor (AR) regulates the development and physiological function of normal prostate as well as the proliferation of cancerous prostate tissue. Treatment with supraphysiological androgen levels (SAL) is used in bipolar androgen therapy and inhibits PCa growth, suggesting SAL induces a tumor suppressive program.

Plasmodium falciparum African PfCRT Mutant Isoforms Conducive to Piperaquine Resistance are Infrequent and Impart a Major Fitness Cost.

Background: Piperaquine, used in combination with dihydroartemisinin, has been identified as a promising partner drug for uncomplicated treatment and chemoprevention of Plasmodium falciparum malaria in Africa. In light of the earlier spread of piperaquine resistance in Southeast Asia, mediated primarily by mutations in the drug efflux transporter PfCRT, we have explored whether PfCRT mutations would represent a probable path to piperaquine resistance becoming established in Africa.

Methods: We edited PfCRT mutations known to mediate piperaquine resistance in Southeast Asia into P.

A potent and selective reaction hijacking inhibitor of Plasmodium falciparum tyrosine tRNA synthetase exhibits single dose oral efficacy in vivo.

The Plasmodium falciparum cytoplasmic tyrosine tRNA synthetase (PfTyrRS) is an attractive drug target that is susceptible to reaction-hijacking by AMP-mimicking nucleoside sulfamates. We previously identified an exemplar pyrazolopyrimidine ribose sulfamate, ML901, as a potent reaction hijacking inhibitor of PfTyrRS. Here we examined the stage specificity of action of ML901, showing very good activity against the schizont stage, but lower trophozoite stage activity.

Inhibitors of malaria parasite cyclic nucleotide phosphodiesterases block asexual blood-stage development and mosquito transmission.

Cyclic nucleotide-dependent phosphodiesterases (PDEs) play essential roles in regulating the malaria parasite life cycle, suggesting that they may be promising antimalarial drug targets. PDE inhibitors are used safely to treat a range of noninfectious human disorders. Here, we report three subseries of fast-acting and potent PDEβ inhibitors that block asexual blood-stage parasite development and that are also active against human clinical isolates.

The part and the whole: how single nodes contribute to large-scale phase-locking in functional EEG networks.

Objective: The application of signal analysis techniques to electroencephalographic (EEG) recordings from epilepsy patients shows that epilepsy involves not only altered neuronal synchronization but also the reorganization of functional EEG networks. This study aims to assess the large-scale phase-locking of such functional networks and how individual network nodes contribute to this collective dynamics.

Methods: We analyze the EEG recorded before, during and after seizures from sixteen patients with pharmacoresistant focal-onset epilepsy.

Genetic interaction mapping of Aurora protein kinases in mouse oocytes.

The Aurora Kinases (AURKs) are a family of serine-threonine protein kinases critical for cell division. Somatic cells express only AURKA and AURKB. However, mammalian germ cells and some cancer cells express all three isoforms.

Linker-specific monoclonal antibodies present a simple and reliable detection method for scFv-based CAR NK cells.

Chimeric antigen receptor (CAR) T cell therapies have demonstrated significant successes in treating cancer. Currently, there are six approved CAR T cell products available on the market that target different malignancies of the B cell lineage. However, to overcome the limitations of CAR T cell therapies, other immune cells are being investigated for CAR-based cell therapies.

Relevance of Continuous EEG versus Routine EEG for Outcome Prediction after Traumatic Brain Injury.

Introduction: In a cohort of adult patients with disturbance of consciousness after TBI, we aimed to explore the relationship of continuous video-EEG (cEEG) versus routine EEG (rEEG) with mortality and functional outcome.

Methods: This is a post hoc analysis of a randomized controlled trial (CERTA), in which adults with disorder of consciousness and needing EEG (excluding those with proven seizures/SE just before) were randomized 1:1 to cEEG or two rEEG. In TBI patients, correlation between EEG duration, mortality, and modified Rankin score (mRs, good 0-2) at 6 months was assessed.

The critical dynamics of hippocampal seizures.

Epilepsy is defined by the abrupt emergence of harmful seizures, but the nature of these regime shifts remains enigmatic. From the perspective of dynamical systems theory, such critical transitions occur upon inconspicuous perturbations in highly interconnected systems and can be modeled as mathematical bifurcations between alternative regimes. The predictability of critical transitions represents a major challenge, but the theory predicts the appearance of subtle dynamical signatures on the verge of instability.

Spatio-temporal requirements of Aurora kinase A in mouse oocyte meiotic spindle building.

Meiotic spindles are critical to ensure chromosome segregation during gamete formation. Oocytes lack centrosomes and use alternative microtubule-nucleation mechanisms for spindle building. How these mechanisms are regulated is still unknown.

The retrotransposon-derived capsid genes and maintain reproductive capacity.

The human genome contains 24 -like capsid genes derived from deactivated retrotransposons conserved among eutherians. Although some of their encoded proteins retain the ability to form capsids and even transfer cargo, their fitness benefit has remained elusive. Here we show that the -like genes and support reproductive capacity during aging.

Predicting Infertility: How Genetic Variants in Oocyte Spindle Genes Affect Egg Quality.

Successful reproduction relies on the union of a single chromosomally normal egg and sperm. Chromosomally normal eggs develop from precursor cells, called oocytes, that have undergone accurate chromosome segregation. The process of chromosome segregation is governed by the oocyte spindle, a unique cytoskeletal machine that splits chromatin content of the meiotically dividing oocyte.

Brief instruments for measuring nutrition literacy - the Nutrition Health Literacy Scale and the Self-Perceived Food Literacy Scale Short Form.

Background: A healthy diet is a critical factor in maintaining long-term health. In addition to a health-promoting food environment, the nutrition health literacy (NHL) and food literacy (FL) of the population are important in this context. This paper describes the development and validation of two short instruments to measure the nutrition literacy of the population, used in the Austrian Nutrition Literacy Survey 2021.

Neuronal current imaging of epileptic activity: An MRI study in patients with a first unprovoked epileptic seizure.

Objective: This study evaluates the performance of the novel MRI sequence stimulus-induced rotary saturation (SIRS) to map responses to interictal epileptic activity in the human cortex. Spin-lock pulses have been applied to indirectly detect neuronal activity through magnetic field perturbations. Following initial reports about the feasibility of the method in humans and animals with epilepsy, we aimed to investigate the diagnostic yield of spin-lock MR pulses in comparison with scalp-EEG in first seizure patients.

Feasibility, Safety, and Performance of Full-Head Subscalp EEG Using Minimally Invasive Electrode Implantation.

Background And Objectives: Current practice in clinical neurophysiology is limited to short recordings with conventional EEG (days) that fail to capture a range of brain (dys)functions at longer timescales (months). The future ability to optimally manage chronic brain disorders, such as epilepsy, hinges upon finding methods to monitor electrical brain activity in daily life. We developed a device for full-head subscalp EEG (Epios) and tested here the feasibility to safely insert the electrode leads beneath the scalp by a minimally invasive technique (primary outcome).

The retrotransposon derived capsid genes and maintain reproductive capacity.

The human genome contains 24 -like capsid genes derived from deactivated retrotransposons conserved among eutherians. Although some of their encoded proteins retain the ability to form capsids and even transfer cargo, their fitness benefit has remained elusive. Here we show that the -like genes and support reproductive capacity.

Multiple intersecting pathways are involved in CPEB1 phosphorylation and regulation of translation during mouse oocyte meiosis.

The RNA-binding protein cytoplasmic polyadenylation element binding 1 (CPEB1) plays a fundamental role in regulating mRNA translation in oocytes. However, the specifics of how and which protein kinase cascades modulate CPEB1 activity are still controversial. Using genetic and pharmacological tools, and detailed time courses, we have re-evaluated the relationship between CPEB1 phosphorylation and translation activation during mouse oocyte maturation.

A conserved germline-specific Dsn1 alternative splice isoform supports oocyte and embryo development.

Alternative mRNA splicing can generate distinct protein isoforms to allow for the differential control of cell processes across cell types. However, alternative splice isoforms that differentially modulate distinct cell division programs have remained elusive. Here, we demonstrate that mammalian germ cells express an alternate mRNA splice isoform for the kinetochore component, DSN1, a subunit of the MIS12 complex that links the centromeres to spindle microtubules during chromosome segregation.

Ultra-Long-Term-EEG Monitoring (ULTEEM) Systems: Towards User-Friendly Out-of-Hospital Recordings of Electrical Brain Signals in Epilepsy.

Epilepsy is characterized by the occurrence of epileptic events, ranging from brief bursts of interictal epileptiform brain activity to their most dramatic manifestation as clinically overt bilateral tonic-clonic seizures. Epileptic events are often modulated in a patient-specific way, for example by sleep. But they also reveal temporal patterns not only on ultra- and circadian, but also on multidien scales.

Influx of zwitterionic buffer after intracytoplasmic sperm injection (ICSI) membrane piercing alters the transcriptome of human oocytes.

Purpose/study Question: Does piercing oocyte membranes during ICSI allow the influx of surrounding zwitterionic buffer into human oocytes and result in altered developmental competence?

Methods: Human oocytes directed to IRB-approved research were used to determine the unrestricted influx of surrounding buffer into the oocyte after piercing of membranes via confocal fluorescence microscopy (n = 80 human MII oocytes) and the influence of the select buffer influx of HEPES, MOPS, and bicarbonate buffer on the oocyte transcriptome using ultra-low input RNA sequencing (n = 40 human MII oocytes).

Results: Piercing membranes of human MII oocytes during sham-ICSI resulted in the unrestricted influx of surrounding culture buffer into the oocyte that was beyond technician control. Transcriptome analysis revealed statistically significant decreased cytoskeletal transcripts in the pierced buffer cohorts, higher levels of embryo competency transcripts (IGF2 and G6PD) in the bicarbonate buffer cohort, higher levels of stress-induced transcriptional repressor transcripts (MAF1) in the HEPES and MOPS cohorts, and decreased levels of numerous chromosomal maintenance transcripts (SMC3) in the HEPES buffer cohort.