Stromal KITL/SCF maintains pancreas tissue homeostasis and restrains tumor progression.

Components of normal tissue architecture serve as barriers to tumor progression. Inflammatory and wound-healing programs are requisite features of solid tumorigenesis, wherein alterations to immune and non-immune stromal elements enable loss of homeostasis during tumor onset. The precise mechanisms by which normal stromal cell states limit tissue plasticity and tumorigenesis, and which are lost during tumor progression, remain largely unknown.

Stromal KITL/SCF promotes pancreas tissue homeostasis and restrains tumor progression.

Components of normal tissue architecture serve as barriers to tumor progression. Inflammatory and wound-healing programs are requisite features of solid tumorigenesis, wherein alterations to immune and non-immune stromal elements enable loss of homeostasis during tumor evolution. The precise mechanisms by which normal stromal cell states limit tissue plasticity and tumorigenesis, and which are lost during tumor progression, remain largely unknown.

Cerebellar Contributions to the Basal Ganglia Influence Motor Coordination, Reward Processing, and Movement Vigor.

Both the cerebellum and the basal ganglia are known for their roles in motor control and motivated behavior. These two systems have been classically considered as independent structures that coordinate their contributions to behavior via separate cortico-thalamic loops. However, recent evidence demonstrates the presence of a rich set of direct connections between these two regions.

Mesenchymal Lineage Heterogeneity Underlies Nonredundant Functions of Pancreatic Cancer-Associated Fibroblasts.

Cancer-associated fibroblast (CAF) heterogeneity is increasingly appreciated, but the origins and functions of distinct CAF subtypes remain poorly understood. The abundant and transcriptionally diverse CAF population in pancreatic ductal adenocarcinoma (PDAC) is thought to arise from a common cell of origin, pancreatic stellate cells (PSC), with diversification resulting from cytokine and growth factor gradients within the tumor microenvironment. Here we analyzed the differentiation and function of PSCs during tumor progression .

Correction: Study of the efficacy of the Hero program: Cross-national evidence.

[This corrects the article DOI: 10.1371/journal.pone.

Study of the efficacy of the Hero program: Cross-national evidence.

The present study focuses on an analysis of the efficacy of the online intervention program called "Hero" for promoting prosociality and other socioemotional variables related to prosocial behavior, such as empathy, positive emotions, and forgiveness, in two Latin American countries: Argentina and Uruguay. The final Argentinean sample consisted of 579 adolescents (experimental group = 319 and control group = 260), and the Uruguayan sample consisted of 330 adolescents (experimental group = 140 and control group = 169), aged 12 to 15 years old. The 'Hero' program provided evidence of efficacy for the promotion of prosociality, empathy, positive emotions, and attitudes of forgiveness.

Collateral Sprouting of Peripheral Sensory Neurons Exhibits a Unique Transcriptomic Profile.

Peripheral nerve injuries result in motor and sensory dysfunction which can be recovered by compensatory or regenerative processes. In situations where axonal regeneration of injured neurons is hampered, compensation by collateral sprouting from uninjured neurons contributes to target reinnervation and functional recovery. Interestingly, this process of collateral sprouting from uninjured neurons has been associated with the activation of growth-associated programs triggered by Wallerian degeneration.

Correction: The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Fibroblast Heterogeneity in the Pancreatic Tumor Microenvironment.

The poor prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) impels an improved understanding of disease biology to facilitate the development of better therapies. PDAC typically features a remarkably dense stromal reaction, featuring and established by a prominent population of cancer-associated fibroblasts (CAF). Genetically engineered mouse models and increasingly sophisticated cell culture techniques have demonstrated important roles for fibroblasts in PDAC progression and therapy response, but these roles are complex, with strong evidence for both tumor-supportive and tumor-suppressive or homeostatic functions.

The necroptosis machinery mediates axonal degeneration in a model of Parkinson disease.

Parkinson's disease (PD) is the second most common neurodegenerative condition, characterized by motor impairment due to the progressive degeneration of dopaminergic neurons in the substantia nigra and depletion of dopamine release in the striatum. Accumulating evidence suggest that degeneration of axons is an early event in the disease, involving destruction programs that are independent of the survival of the cell soma. Necroptosis, a programmed cell death process, is emerging as a mediator of neuronal loss in models of neurodegenerative diseases.

Cementoplasty of pelvic bone metastases: systematic assessment of lesion filling and other factors that could affect the clinical outcomes.

Objectives: To evaluate lesion filling and other factors that could affect the clinical outcomes of cementoplasty for pelvic bone metastases.

Methods: We retrospectively reviewed the files of 40 patients treated for 44 pelvic bone metastases, collected the parameters related to patients (pain relief evaluated on a visual analog scale, subsequent fractures, and need for surgery), lesions (size, cortical breach score, fracture, soft-tissue extension), and cementoplasty procedures (number of needles, volume of cement, percentage of lesion filling, cement leaks, residual acetabular roof defect), and performed a statistical analysis.

Results: The lesions were on average 43.

A Molecular Reporter for Monitoring Autophagic Flux in Nervous System In Vivo.

The relevance of autophagy in neuronal health has been extensively reported in a plethora of conditions affecting the nervous system, such as neurodegenerative diseases, cancer, diabetes, and tissue injury, where altered autophagic activity may contribute to the pathological process. Autophagy is a dynamic pathway involving the formation of a membrane surrounding and enclosing cargoes that are delivered to lysosomal compartments for degradation. Cargoes can include large protein aggregates, organelles, or even pathogens.

Injury to the nervous system: A look into the ER.

Injury to the central or peripheral nervous systems leads to the loss of cognitive and/or sensorimotor capabilities that still lack an effective treatment. Although injury to the nervous system involves multiple and complex molecular factors, alteration to protein homeostasis is emerging as a relevant pathological mechanism. In particular, chronic endoplasmic reticulum (ER) stress is proposed as a possible driver of neuronal dysfunction in conditions such as spinal cord injury, stroke and damage to peripheral nerves.

Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury.

Although protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models of spinal cord injury and neurodegeneration, the contribution of this pathway to peripheral nerve damage remains poorly explored. Here we targeted the unfolded protein response (UPR), an adaptive reaction against ER stress, in mouse models of sciatic nerve injury and found that ablation of the transcription factor XBP1, but not ATF4, significantly delay locomotor recovery. XBP1 deficiency led to decreased macrophage recruitment, a reduction in myelin removal and axonal regeneration.

Dysregulated co-stimulatory molecule expression in a Sjögren's syndrome mouse model with potential implications by microRNA-146a.

Sjögren's syndrome (SjS) is an autoimmune condition that primarily affects salivary and lacrimal glands, causing loss of secretion. We have previously shown that microRNA-146a (miR-146a) is over-expressed in the salivary glands and peripheral blood mononuclear cells (PBMC) of SjS-prone mice (C57BL/6.NOD-Aec1Aec2, B6DC) and in PBMC of SjS patients.

Functional Role of the Disulfide Isomerase ERp57 in Axonal Regeneration.

ERp57 (also known as grp58 and PDIA3) is a protein disulfide isomerase that catalyzes disulfide bonds formation of glycoproteins as part of the calnexin and calreticulin cycle. ERp57 is markedly upregulated in most common neurodegenerative diseases downstream of the endoplasmic reticulum (ER) stress response. Despite accumulating correlative evidence supporting a neuroprotective role of ERp57, the contribution of this foldase to the physiology of the nervous system remains unknown.

Measurement of autophagy flux in the nervous system in vivo.

Accurate methods to measure autophagic activity in vivo in neurons are not available, and most of the studies are based on correlative and static measurements of autophagy markers, leading to conflicting interpretations. Autophagy is an essential homeostatic process involved in the degradation of diverse cellular components including organelles and protein aggregates. Autophagy impairment is emerging as a relevant factor driving neurodegeneration in many diseases.

Yeast-based assay identifies novel Shh/Gli target genes in vertebrate development.

Background: The increasing number of developmental events and molecular mechanisms associated with the Hedgehog (Hh) pathway from Drosophila to vertebrates, suggest that gene regulation is crucial for diverse cellular responses, including target genes not yet described. Although several high-throughput, genome-wide approaches have yielded information at the genomic, transcriptional and proteomic levels, the specificity of Gli binding sites related to direct target gene activation still remain elusive. This study aims to identify novel putative targets of Gli transcription factors through a protein-DNA binding assay using yeast, and validating a subset of targets both in-vitro and in-vivo.