Using in vivo intact structure for system-wide quantitative analysis of changes in proteins.

Mass spectrometry-based methods can provide a global expression profile and structural readout of proteins in complex systems. Preserving the in vivo conformation of proteins in their innate state is challenging during proteomic experiments. Here, we introduce a whole animal in vivo protein footprinting method using perfusion of reagents to add dimethyl labels to exposed lysine residues on intact proteins which provides information about protein conformation.

Revealing the Novel Role of Purinergic Receptor P2X4 in Phagocytic Uptake After Ischemic Stroke.

Background: Purinergic receptor P2X4 (P2X4R), highly expressed on microglia and macrophages, is activated by ATP released from damaged cells and linked to poststroke inflammation. Previous studies showed that short-term P2X4R inhibition reduces inflammation and promotes long term recovery, but the mechanism underlying P2X4R and inflammation remains unclear. We hypothesized that P2X4R absence or pharmacological blockade can enhance macrophage phagocytic function by alleviating excessive inflammation after stroke.

Repeated Binge Alcohol Drinking Leads to Reductions in Corticostriatal Theta Coherence in Female but not Male Mice.

Decreased functional connectivity between the striatum and frontal cortex is observed in individuals with alcohol use disorder (AUD), and predicts the probability of relapse in abstinent individuals with AUD. To further our understanding of how repeated alcohol (ethanol; EtOH) consumption impacts the corticostriatal circuit, extracellular electrophysiological recordings (local field potentials; LFPs) were gathered from the nucleus accumbens (NAc) and prefrontal cortex (PFC) of C57BL/6J mice voluntarily consuming EtOH or water using a 'drinking-in-the-dark' (DID) procedure. Following a three-day acclimation period wherein only water access was provided during DID, mice were given 15 consecutive days of access to EtOH.

ALS-derived fibroblasts exhibit reduced proliferation rate, cytoplasmic TDP-43 aggregation and a higher susceptibility to DNA damage.

Background: Dermic fibroblasts have been proposed as a potential genetic-ALS cellular model. This study aimed to explore whether dermic fibroblasts from patients with sporadic-ALS (sALS) recapitulate alterations typical of ALS motor neurons and exhibit abnormal DNA-damage response.

Methods: Dermic fibroblasts were obtained from eight sALS patients and four control subjects.

Urbanization in Sub-Saharan Africa: Declining Rates of Chronic and Recurrent Infection and Their Possible Role in the Origins of Non-communicable Diseases.

Background: Non-communicable diseases (NCDs), such as atherosclerosis and cancers, are a leading cause of death worldwide. An important, yet poorly explained epidemiological feature of NCDs is their low incidence in under developed areas of low-income countries and rising rates in urban areas.

Methods: With the goal of better understanding how urbanization increases the incidence of NCDs, we provide an overview of the urbanization process in sub-Saharan Africa, discuss gene expression differences between rural and urban populations, and review the current NCD determinant model.

Effects of preoperative statin use on perioperative outcomes of carotid endarterectomy.

Objectives: Several studies have shown the beneficial role of statins in reducing the risk of major perioperative complications and death associated with noncardiac vascular surgery, but few have focused on their effects in the event of carotid endarterectomy (CEA). This study analyzes the effects of preoperative statin use on perioperative outcomes in patients undergoing CEA.

Materials And Methods: Data from all consecutive patients who underwent primary CEA for symptomatic and asymptomatic carotid disease between 2002 and 2014 at a single institution were prospectively stored in a vascular surgery registry, recording risk factors, medication, and indication for surgery.

A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to β-Cell Mitochondrial Dysfunction in Type 2 Diabetes.

Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21).

ABCA1 is Necessary for Bexarotene-Mediated Clearance of Soluble Amyloid Beta from the Hippocampus of APP/PS1 Mice.

Alzheimer's disease (AD) is characterized by impaired clearance of amyloid beta (Aβ) peptides, leading to the accumulation of Aβ in the brain and subsequent neurodegeneration and cognitive impairment. ApoE plays a critical role in the proteolytic degradation of soluble forms of Aβ. This effect is dependent upon lipidation of ApoE by ABCA1-mediated transfer of phospholipids and cholesterol.

Distribution and innervation of taste buds in the axolotl.

Adult axolotls have approximately 1,400 taste buds in the epithelium of the pharyngeal roof and floor and the medial surfaces of the visceral bars. These receptors are most dense on the lingual surfaces of the upper and lower jaws, slightly less dense throughout lateral portions of the pharyngeal roof and floor, and more sparse within medial portions of the pharyngeal roof and floor, except for a median oval patch of receptors located rostrally between the vomerine tooth fields. Each taste bud is a pear-shaped organ, situated at the center of a raised hillock and averaging 80 and 87 microm in height and width, respectively.

Alz-50 recognizes a phosphorylated epitope of tau protein.

Alz-50 is a monoclonal antibody that detects antigens enriched in the brain tissue of Alzheimer's disease (AD) patients. Although Alz-50 recognizes tau, an identified integral constituent of the AD paired helical filament (PHF), the exact nature of the antigenic site is unknown. An immunoblot analysis demonstrated that the antigenic sites to Alz-50 are diminished by acid phosphatase treatment.