The role of sigma 1 receptor in organization of endoplasmic reticulum signaling microdomains.

Sigma 1 receptor (S1R) is a 223-amino-acid-long transmembrane endoplasmic reticulum (ER) protein. S1R modulates activity of multiple effector proteins and is a well-established drug target. However, signaling functions of S1R in cells are poorly understood.

Normalization of Calcium Balance in Striatal Neurons in Huntington's Disease: Sigma 1 Receptor as a Potential Target for Therapy.

Huntington's disease (HD) is a neurodegenerative, dominantly inherited genetic disease caused by expansion of the polyglutamine tract in the huntingtin gene. At the cellular level, HD is characterized by the accumulation of mutant huntingtin protein in brain cells, resulting in the development of the HD phenotype, which includes mental disorders, decreased cognitive abilities, and progressive motor impairments in the form of chorea. Despite numerous studies, no unambigous connection between the accumulation of mutant protein and selective death of striatal neurons has yet been established.

Lumbar Bracing for Chronic Low Back Pain: A Randomized Controlled Trial.

Purpose: We performed this study to evaluate the effect of back bracing to treat patients with chronic low back pain.

Methods: This was a prospective, unblinded, randomized controlled trial of 61 adults with uncomplicated chronic low back pain (>12 wks) and imaging findings of degenerative spondylosis, to assess the effectiveness of a semirigid back brace. All study participants received back school instruction.

CLEAR - Medical use of contact lenses.

The medical use of contact lenses is a solution for many complex ocular conditions, including high refractive error, irregular astigmatism, primary and secondary corneal ectasia, disfiguring disease, and ocular surface disease. The development of highly oxygen permeable soft and rigid materials has extended the suitability of contact lenses for such applications. There is consistent evidence that bandage soft contact lenses, particularly silicone hydrogel lenses, improve epithelial healing and reduce pain in persistent epithelial defects, after trauma or surgery, and in corneal dystrophies.

The role of Bcl-2 proteins in modulating neuronal Ca signaling in health and in Alzheimer's disease.

The family of B-cell lymphoma-2 (Bcl-2) proteins exerts key functions in cellular health. Bcl-2 primarily acts in mitochondria where it controls the initiation of apoptosis. However, during the last decades, it has become clear that this family of proteins is also involved in controlling intracellular Ca signaling, a critical process for the function of most cell types, including neurons.

Balancing ER-Mitochondrial Ca Fluxes in Health and Disease.

Organelles cooperate with each other to control cellular homeostasis and cell functions by forming close connections through membrane contact sites. Important contacts are present between the endoplasmic reticulum (ER), the main intracellular Ca-storage organelle, and the mitochondria, the organelle responsible not only for the majority of cellular ATP production but also for switching on cell death processes. Several Ca-transport systems focalize at these contact sites, thereby enabling the efficient transmission of Ca signals from the ER toward mitochondria.

A detailed characterization of stepwise activation of the androgen receptor variant 7 in prostate cancer cells.

Expression of the androgen receptor splice variant 7 (AR-V7) is frequently detected in castrate resistant prostate cancer and associated with resistance to AR-targeted therapies. While we have previously noted that homodimerization is required for the transcriptional activity of AR-V7 and that AR-V7 can also form heterodimers with the full-length AR (AR-FL), there are still many gaps of knowledge in AR-V7 stepwise activation. In the present study, we show that neither AR-V7 homodimerization nor AR-V7/AR-FL heterodimerization requires cofactors or DNA binding.

Synthesis and fluorine-18 radiolabeling of a phospholipid as a PET imaging agent for prostate cancer.

Introduction: Altered lipid metabolism and subsequent changes in cellular lipid composition have been observed in prostate cancer cells, are associated with poor clinical outcome, and are promising targets for metabolic therapies. This study reports for the first time on the synthesis of a phospholipid radiotracer based on the phospholipid 1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine (PC44:12) to allow tracking of polyunsaturated lipid tumor uptake via PET imaging. This tracer may aid in the development of strategies to modulate response to therapies targeting lipid metabolism in prostate cancer.

Dendritic Spines Shape Analysis-Classification or Clusterization? Perspective.

Dendritic spines are small protrusions from the dendrite membrane, where contact with neighboring axons is formed in order to receive synaptic input. Changes in size, shape, and density of synaptic spines are associated with learning and memory, and observed after drug abuse in a variety of neurodegenerative, neurodevelopmental, and psychiatric disorders. Due to the preeminent importance of synaptic spines, there have been major efforts into developing techniques that enable visualization and analysis of dendritic spines in cultured neurons, in fixed slices and in intact brain tissue.

Leptin Receptors in RIP-Cre Neurons Mediate Anti-dyslipidemia Effects of Leptin in Insulin-Deficient Mice.

Leptin is a potent endocrine hormone produced by adipose tissue and regulates a broad range of whole-body metabolism such as glucose and lipid metabolism, even without insulin. Central leptin signaling can lower hyperglycemia in insulin-deficient rodents via multiple mechanisms, including improvements of dyslipidemia. However, the specific neurons that regulate anti-dyslipidemia effects of leptin remain unidentified.

Acetaminophen Toxicity: A History of Serendipity and Unintended Consequences.

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In-hospital mortality and morbidity among extremely preterm infants in relation to maternal body mass index.

Objective: The objective of this paper is to compare in-hospital survival and survival without major morbidities in extremely preterm infants in relation to maternal body mass index (BMI).

Methods: This retrospective cohort study included extremely preterm infants (gestational age 22-28 weeks). This study was conducted at National Institute of Child Health and Human Development Neonatal Research Network sites.

Placental transfusion and short-term outcomes among extremely preterm infants.

Objective: To compare short-term outcomes after placental transfusion (delayed cord clamping (DCC) or umbilical cord milking (UCM)) versus immediate cord clamping among extremely preterm infants.

Design: Retrospective study.

Setting: The National Institute of Child Health and Human Development Neonatal Research Network registry.

The macrophage activation marker soluble CD163 is elevated and associated with liver disease phenotype in patients with Wilson's disease.

Background: Macrophages play a significant role in liver disease development and progression. The macrophage activation marker soluble (s)CD163 is associated with severity and prognosis in a number of different acute and chronic liver diseases but has been only sparsely examined in Wilson's disease (WD). We investigated sCD163 levels in patients with acute and chronic WD and hypothesized associations with liver disease phenotype and biochemical markers of liver injury.

Advances in biomarker development in acetaminophen toxicity.

Acetaminophen liver injury is the most common cause of acute liver injury in the United States and several other countries. Diagnosis of acetaminophen-induced acute liver injury in the clinic is challenging due to the lack of validated and specific biomarkers. The following chapter provides an overview of recent advances evaluating candidate biomarkers in development for acetaminophen acute liver injury.

Crystal structure of the SH3 domain of growth factor receptor-bound protein 2.

This study presents the crystal structure of the N-terminal SH3 (SH3N) domain of growth factor receptor-bound protein 2 (Grb2) at 2.5 Å resolution. Grb2 is a small (215-amino-acid) adaptor protein that is widely expressed and involved in signal transduction/cell communication.

A novel functional cross-interaction between opioid and pheromone signaling may be involved in stress avoidance in Caenorhabditis elegans.

Upon sensing starvation stress, Caenorhabditis elegans larvae (L2d) elicit two seemingly opposing behaviors to escape from the stressful condition: food-seeking roaming mediated by the opioid peptide NLP-24 and dauer formation mediated by pheromones. Because opioid and pheromone signals both originate in ASI chemosensory neurons, we hypothesized that they might act sequentially or competitively to avoid starvation stress. Our data shows that NPR-17 opioid receptor signaling suppressed pheromone biosynthesis and the overexpression of opioid genes disturbed dauer formation.

Optimizing oxygen therapy for preterm infants at birth: Are we there yet?

Premature infants undergo a complex postnatal adaptation at birth. For last two centuries, oxygen has been integral to respiratory support of preterm infants at birth. Excess oxygen can cause oxidative stress and tissue injury.

Acute Liver Failure (ALF) in Pregnancy: How Much Is Pregnancy Related?

Background And Aims: Acute liver failure (ALF), characterized by sudden onset of coagulopathy (international normalized ratio [INR] ≥ 1.5) and encephalopathy, may occur during pregnancy either as a pregnancy-associated etiology or an unrelated and coincidental liver injury. The U.

Critical Role of Matrix Metalloproteinase 14 in Adipose Tissue Remodeling during Obesity.

Fibrosis is recognized as the major pathological change in adipose tissue during the development of obesity. However, the detailed mechanisms governing the interactions between the fibrotic components and their modifiers remain largely unclear. Here, we reported that matrix metalloproteinase 14 (MMP14), a key pericellular collagenase, is dramatically upregulated in obese adipose tissue.

Oxygen for respiratory support of moderate and late preterm and term infants at birth: Is air best?

Oxygen has been used for newborn infant resuscitation for more than two centuries. In the last two decades, concerns about oxidative stress and injury have changed this practice. Air (FiO 0.