Opportunities for System Neuroscience.

Systems neuroscience explores the intricate organization and dynamic function of neural circuits and networks within the brain. By elucidating how these complex networks integrate to execute mental operations, this field aims to deepen our understanding of the biological basis of cognition, behavior, and consciousness. In this chapter, we outline the promising future of systems neuroscience, highlighting the emerging opportunities afforded by powerful technological innovations and their applications.

DNA cytosine methyltransferases differentially regulate genome-wide hypermutation and interhomolog recombination in Trichoderma reesei meiosis.

Trichoderma reesei is an economically important enzyme producer with several unique meiotic features. spo11, the initiator of meiotic double-strand breaks (DSBs) in most sexual eukaryotes, is dispensable for T. reesei meiosis.

One- and 2-year outcomes of lumbar facet arthroplasty versus spinal fusion in young (<65 years) and old (≥65 years) patients for the treatment of degenerative spondylolisthesis and stenosis.

Background: Facet arthroplasty, an alternative to lumbar fusion, offers stabilization and preserves range of motion. This subanalysis of the TOPS IDE trial (FDA #G160168) compared facet arthroplasty, using the TOPS device, with a standard single-level transforaminal lumbar interbody fusion (TLIF) in patients stratified by age (<65 and ≥65 years) with symptomatic grade 1 degenerative spondylolisthesis with moderate to severe spinal stenosis at L2-5.

Methods: Patient-reported outcomes (PROMS), including Oswestry disability index (ODI), visual analog pain scales (VAS), and Zurich claudication questionnaires (ZCQ), were assessed at baseline and multiple postoperative timepoints.

Timeless noncoding DNA contains cell-type preferential enhancers important for proper Drosophila circadian regulation.

To address the contribution of transcriptional regulation to clock gene expression and to behavior, we generated a series of CRISPR-mediated deletions within two regions of the circadian gene (), an intronic E-box region and an upstream E-box region that are both recognized by the key transcription factor Clock (Clk) and its heterodimeric partner Cycle. The upstream deletions but not an intronic deletion dramatically impact expression in fly heads; the biggest upstream deletion reduces peak RNA levels and RNA cycling amplitude to about 15% of normal, and there are similar effects on protein (TIM). The cycling amplitude of other clock genes is also strongly reduced, in these cases due to increases in trough levels.

A novel PDPN antagonist peptide CY12-RP2 inhibits melanoma growth via Wnt/β-catenin and modulates the immune cells.

Background: Podoplanin (PDPN) is a highly conserved, mucin-type protein specific to the lymphatic system. Overexpression of PDPN is associated with the progression of various solid tumors, and plays an important roles in the tumor microenvironment by regulating the immune system. However, the role of PDPN-mediated signal activation in the progression of melanoma is still unknown.

The neurosurgeon workforce: a geographical gender-focused analysis of the trends in representation of neurosurgeons and choices in training over 70 years.

Objective: Neurosurgeons frequently move throughout their careers, with moves driven by personal and professional factors. In this study, the authors analyzed these migration trends through a dynamic migratory map and statistical review, with a particular focus on differences in education and practice patterns between male and female neurosurgeons.

Methods: A list containing all board-certified and -affiliated US neurosurgeons practicing in 2019 was obtained from the American Association of Neurological Surgeons.

FANCI is Associated with Poor Prognosis and Immune Infiltration in Liver Hepatocellular Carcinoma.

This study aimed to validate FANCI as a potential marker for both prognosis and therapy in liver hepatocellular carcinoma. FANCI expression data were acquired from GEPIA, HPA, TCGA, and GEO databases. The impact of clinicopathological features was analyzed by UALCAN.

Widespread posttranscriptional regulation of cotransmission.

While neurotransmitter identity was once considered singular and immutable for mature neurons, it is now appreciated that one neuron can release multiple neuroactive substances (cotransmission) whose identities can even change over time. To explore the mechanisms that tune the suite of transmitters a neuron releases, we developed transcriptional and translational reporters for cholinergic, glutamatergic, and GABAergic signaling in . We show that many glutamatergic and GABAergic cells also transcribe cholinergic genes, but fail to accumulate cholinergic effector proteins.

Butt-seq: a new method for facile profiling of transcription.

A wide range of sequencing methods has been developed to assess nascent RNA transcription and resolve the single-nucleotide position of RNA polymerase genome-wide. These techniques are often burdened with high input material requirements and lengthy protocols. We leveraged the template-switching properties of thermostable group II intron reverse transcriptase (TGIRT) and developed Butt-seq (bulk analysis of nascent transcript termini sequencing), which can produce libraries from purified nascent RNA in 6 h and from as few as 10,000 cells-an improvement of at least 10-fold over existing techniques.

All-Cause and Cardiovascular-Related Mortality in CKD Patients With and Without Heart Failure: A Population-Based Cohort Study in Kaiser Permanente Southern California.

Rationale & Objective: Heart failure and chronic kidney disease (CKD) frequently coexist reflective of the strong interplay between these organ systems. A better understanding of the prevalence of different types of heart failure (preserved and reduced ejection fraction) and their subsequent mortality risks among advanced CKD patients would provide important epidemiologic insights and may pave the way for more focused and proactive management strategies.

Study Design: Retrospective cohort study.

Widespread post-transcriptional regulation of co-transmission.

Unlabelled: While neurotransmitter identity was once considered singular and immutable for mature neurons, it is now appreciated that one neuron can release multiple neuroactive substances (co-transmission) whose identities can even change over time. To explore the mechanisms that tune the suite of transmitters a neuron releases, we developed transcriptional and translational reporters for cholinergic, glutamatergic, and GABAergic signaling in . We show that many glutamatergic and GABAergic cells also transcribe cholinergic genes, but fail to accumulate cholinergic effector proteins.

Nano-LYTACs for Degradation of Membrane Proteins and Inhibition of CD24/Siglec-10 Signaling Pathway.

Lysosome-targeting chimeras (LYTACs) are an emerging therapeutic modality that effectively degrade cancer cell membranes and extracellular target proteins. In this study, a nanosphere-based LYTAC degradation system is developed. The amphiphilic peptide-modified N-acetylgalactosamine (GalNAc) can self-assemble into nanospheres with a strong affinity for asialoglycoprotein receptor targets.

Correction: Yu et al. Recent Advances of Mesoporous Silica as a Platform for Cancer Immunotherapy. 2022, , 109.

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Peptide-based PROTAC degrader of FOXM1 suppresses cancer and decreases GLUT1 and PD-L1 expression.

Background: Peptide proteolysis-targeting chimeras (p-PROTACs) with advantages of high specificity and low toxicity have emerged as a powerful technology of targeted protein degradation for biomedical applications. FOXM1, a proliferation-associated transcription factor, is overexpressed in a variety of human tumors as a key driver of tumorigenesis and cancer progression, and is a potential anticancer therapeutic target. However, FOXM1-targeting p-PROTACs has not been researched.

Real-world use patterns of angiotensin receptor-neprilysin inhibitor (sacubitril/valsartan) among patients with heart failure within a large integrated health system.

Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) that is now preferred in guidelines over angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for patients with heart failure with reduced ejection fraction (HFrEF). However, it has not been broadly adopted in clinical practice. To characterize ARNI use within a large diverse real-world population and assess for any racial disparities.

Disease-Specific Factors Associated with Readmissions or Mortality After Hospital Discharge in COVID-19 Patients: a Retrospective Cohort Study.

Background: Understanding the implications of disease-specific factors beyond baseline patient characteristics for coronavirus disease 2019 (COVID-19) may allow for identification of indicators for safe hospital discharge.

Objective: Assess whether disease-specific factors are associated with adverse events post-discharge using a data-driven approach.

Design: Retrospective cohort study.

Statin Use and Mortality among Patients Hospitalized with Sepsis: A Retrospective Cohort Study within Southern California, 2008-2018.

Background: Despite early goal-directed therapy, sepsis mortality remains high. Statins exhibit pleiotropic effects.

Objective: We sought to compare mortality outcomes among statin users versus nonusers who were hospitalized with sepsis.

TRPM2 deficiency in mice protects against atherosclerosis by inhibiting TRPM2-CD36 inflammatory axis in macrophages.

Atherosclerosis is the major cause of ischemic heart disease and stroke, the leading causes of mortality worldwide. The central pathological features of atherosclerosis include macrophage infiltration and foam cell formation. However, the detailed mechanisms regulating these two processes remain unclear.

Functional coupling of TRPM2 and extrasynaptic NMDARs exacerbates excitotoxicity in ischemic brain injury.

Excitotoxicity induced by NMDA receptor (NMDAR) activation is a major cause of neuronal death in ischemic stroke. However, past efforts of directly targeting NMDARs have unfortunately failed in clinical trials. Here, we reveal an unexpected mechanism underlying NMDAR-mediated neurotoxicity, which leads to the identification of a novel target and development of an effective therapeutic peptide for ischemic stroke.