Proteomics-on-a-Chip - Microfluidics meets proteomics.

Proteomics provides an understanding of biological systems by enabling the detailed study of protein expression profiles, which is crucial for early disease diagnosis. Microfluidic-based proteomics enhances this field by integrating complex proteome analysis into compact and efficient systems. This review focuses on developing microfluidic chip structures for proteomics, covering on-chip sample pretreatment, protein extraction, purification, and identification in recent years.

False-Negative Review from the Mammography Audit: Refining Breast Imaging Practice.

Annual review of false-negative (FN) mammograms is a mandatory and critical component of the Mammography Quality Standards Act (MQSA) annual mammography audit. FN review can help hone reading skills and improve the ability to detect cancers at mammography. Subtle architectural distortion, asymmetries (seen only on one view), small lesions, lesions with probably benign appearance (circumscribed regular borders), isolated microcalcifications, and skin thickening are the most common mammographic findings when the malignancy is visible at retrospective review of FN mammograms.

Identification of polycystin 2 missense mutants targeted for endoplasmic reticulum-associated degradation.

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder leading to end-stage renal disease. ADPKD arises from mutations in the and genes, which encode polycystin 1 (PC1) and polycystin 2 (PC2), respectively. PC2 is a nonselective cation channel, and disease-linked mutations disrupt normal cellular processes, including signaling and fluid secretion.

Microfluidics chips fabrication techniques comparison.

This study investigates various microfluidic chip fabrication techniques, highlighting their applicability and limitations in the context of urgent diagnostic needs showcased by the COVID-19 pandemic. Through a detailed examination of methods such as computer numerical control milling of a polymethyl methacrylate, soft lithography for polydimethylsiloxane-based devices, xurography for glass-glass chips, and micromachining-based silicon-glass chips, we analyze each technique's strengths and trade-offs. Hence, we discuss the fabrication complexity and chip thermal properties, such as heating and cooling rates, which are essential features of chip utilization for a polymerase chain reaction.

Excess dietary sodium restores electrolyte and water homeostasis caused by loss of the endoplasmic reticulum molecular chaperone, GRP170, in the mouse nephron.

The maintenance of fluid and electrolyte homeostasis by the kidney requires proper folding and trafficking of ion channels and transporters in kidney epithelia. Each of these processes requires a specific subset of a diverse class of proteins termed molecular chaperones. One such chaperone is GRP170, which is an Hsp70-like, endoplasmic reticulum (ER)-localized chaperone that plays roles in protein quality control and protein folding in the ER.

Assays to measure small molecule Hsp70 agonist activity in vitro and in vivo.

Hsp70 prevents protein aggregation and is cytoprotective, but sustained Hsp70 overexpression is problematic. Therefore, we characterized small molecule agonists that augment Hsp70 activity. Because cumbersome assays were required to assay agonists, we developed cell-based and in vivo assays in which disease-associated consequences of Hsp70 activation can be quantified.

Exploring the Frontiers of Cell Temperature Measurement and Thermogenesis.

The precise measurement of cell temperature and an in-depth understanding of thermogenic processes are critical in unraveling the complexities of cellular metabolism and its implications for health and disease. This review focuses on the mechanisms of local temperature generation within cells and the array of methods developed for accurate temperature assessment. The contact and noncontact techniques are introduced, including infrared thermography, fluorescence thermometry, and other innovative approaches to localized temperature measurement.

Principles of Lesser Toe and Metatarsophalangeal Joint Reconstruction for Complex and Revision Surgery of the Forefoot.

Successful lesser toes and metatarsophalangeal (MTP) joint reconstruction must withstand substantial biomechanical loads from standing, walking, and exercise. While complications following lesser toe and MTP reconstruction are common, limited literature addresses revision surgeries for complications including recurrence. Numerous complications of surgery for toes and lesser MTP joints can be managed or improved through revision surgery, but not all complications can be prevented or resolved.

FITM2 deficiency results in ER lipid accumulation, ER stress, and reduced apolipoprotein B lipidation and VLDL triglyceride secretion in vitro and in mouse liver.

Objective: Triglycerides (TGs) associate with apolipoprotein B100 (apoB100) to form very low density lipoproteins (VLDLs) in the liver. The repertoire of factors that facilitate this association is incompletely understood. FITM2, an integral endoplasmic reticulum (ER) protein, was originally discovered as a factor participating in cytosolic lipid droplet (LD) biogenesis in tissues that do not form VLDL.

The emerging role of fat-inducing transcript 2 in endoplasmic reticulum proteostasis and lipoprotein biogenesis.

Purpose Of Review: This review examines the evolving role of the fat-inducing transcript 2 (FIT2) protein in lipid droplet (LD) biology and its broader implications in cellular physiology and disease. With recent advancements in understanding FIT2 function across various model systems, this review provides a timely synthesis of its mechanisms and physiological significance.

Recent Findings: FIT2, an endoplasmic reticulum (ER)-resident protein, has been established as a critical regulator of LD formation in diverse organisms, from yeast to mammals.

Current insights and assumptions on α-synuclein in Lewy body disease.

Lewy body disorders are heterogeneous neurological conditions defined by intracellular inclusions composed of misshapen α-synuclein protein aggregates. Although α-synuclein aggregates are only one component of inclusions and not strictly coupled to neurodegeneration, evidence suggests they seed the propagation of Lewy pathology within and across cells. Genetic mutations, genomic multiplications, and sequence polymorphisms of the gene encoding α-synuclein are also causally linked to Lewy body disease.

Characterization of hyperactive mutations in the renal potassium channel ROMK uncovers unique effects on channel biogenesis and ion conductance.

Hypertension affects one billion people worldwide and is the most common risk factor for cardiovascular disease, yet a comprehensive picture of its underlying genetic factors is incomplete. Amongst regulators of blood pressure is the renal outer medullary potassium (ROMK) channel. While select ROMK mutants are prone to premature degradation and lead to disease, heterozygous carriers of some of these same alleles are protected from hypertension.

The biogenesis of potassium transporters: implications of disease-associated mutations.

The concentration of intracellular and extracellular potassium is tightly regulated due to the action of various ion transporters, channels, and pumps, which reside primarily in the kidney. Yet, potassium transporters and cotransporters play vital roles in all organs and cell types. Perhaps not surprisingly, defects in the biogenesis, function, and/or regulation of these proteins are linked to range of catastrophic human diseases, but to date, few drugs have been approved to treat these maladies.

The HERCulean task of recognizing, ubiquitinating, and shielding misfolded integral membrane proteins.

During ER-associated decay, unfolded membrane-resident proteins are targeted for removal and degradation by ubiquitin ligases whose identities and precise operations remain unclear. In this issue, Guerriero and Brodsky discuss new results from Kamada et al. (https://doi.

Comparing Video Head Impulse Testing With Rotary Chair in Pediatric Patients: A Controlled Trial.

Objectives: To investigate the efficacy of video head impulse testing (VHIT) in detecting vestibular loss in pediatric patients with abnormal rotary chair testing, compared to a control group with normal rotary chair testing.

Study Design: Prospective, nonrandomized, controlled trial.

Setting: Pediatric vestibular program at tertiary level children's hospital.

Optimization of the fluorogen-activating protein tag for quantitative protein trafficking and co-localization studies in S. cerevisiae.

Spatial and temporal tracking of fluorescent proteins in live cells permits visualization of proteome remodeling in response to extracellular cues. Historically, protein dynamics during trafficking have been visualized using constitutively active fluorescent proteins (FPs) fused to proteins of interest. While powerful, such FPs label all cellular pools of a protein, potentially masking the dynamics of select subpopulations.

Vertical organic electrochemical transistor platforms for efficient electropolymerization of thiophene based oligomers.

Organic electrochemical transistors (OECTs) have emerged as promising candidates for various fields, including bioelectronics, neuromorphic computing, biosensors, and wearable electronics. OECTs operate in aqueous solutions, exhibit high amplification properties, and offer ion-to-electron signal transduction. The OECT channel consists of a conducting polymer, with PEDOT:PSS receiving the most attention to date.

Loss of Grp170 results in catastrophic disruption of endoplasmic reticulum function.

GRP170 () is required for mouse embryonic development, and its ablation in kidney nephrons leads to renal failure. Unlike most chaperones, GRP170 is the lone member of its chaperone family in the ER lumen. However, the cellular requirement for GRP170, which both binds nonnative proteins and acts as nucleotide exchange factor for BiP, is poorly understood.

Parylene-bonded micro-fluidic channels for cryogenic experiments at superfluid He-4 temperatures.

We present the manufacturing process of a (24.5 × 100) μm2-sized on-chip flow channel intended for flow experiments with normal and superfluid phases of 4He and showcase such a proof-of-concept experiment. This work proves the suitability of chip-to-chip bonding using a thin layer of Parylene-C for cryogenic temperatures as a simpler alternative to other techniques, such as anodic bonding.

The expression system influences stability, maturation efficiency, and oligomeric properties of the potassium-chloride co-transporter KCC2.

The neuron-specific K/Cl co-transporter 2, KCC2, which is critical for brain development, regulates γ-aminobutyric acid-dependent inhibitory neurotransmission. Consistent with its function, mutations in KCC2 are linked to neurodevelopmental disorders, including epilepsy, schizophrenia, and autism. KCC2 possesses 12 transmembrane spans and forms an intertwined dimer.

J-domain proteins: From molecular mechanisms to diseases.

J-domain proteins (JDPs) are the largest family of chaperones in most organisms, but much of how they function within the network of other chaperones and protein quality control machineries is still an enigma. Here, we report on the latest findings related to JDP functions presented at a dedicated JDP workshop in Gdansk, Poland. The report does not include all (details) of what was shared and discussed at the meeting, because some of these original data have not yet been accepted for publication elsewhere or represented still preliminary observations at the time.

Excess dietary sodium partially restores salt and water homeostasis caused by loss of the endoplasmic reticulum molecular chaperone, GRP170, in the mouse nephron.

The maintenance of fluid and electrolyte homeostasis by the kidney requires proper folding and trafficking of ion channels and transporters in kidney epithelia. Each of these processes requires a specific subset of a diverse class of proteins termed molecular chaperones. One such chaperone is GRP170, which is an Hsp70-like, endoplasmic reticulum (ER)-localized chaperone that plays roles in protein quality control and protein folding in the ER.

The Essential Functions of Molecular Chaperones and Folding Enzymes in Maintaining Endoplasmic Reticulum Homeostasis.

It has been estimated that up to one-third of the proteins encoded by the human genome enter the endoplasmic reticulum (ER) as extended polypeptide chains where they undergo covalent modifications, fold into their native structures, and assemble into oligomeric protein complexes. The fidelity of these processes is critical to support organellar, cellular, and organismal health, and is perhaps best underscored by the growing number of disease-causing mutations that reduce the fidelity of protein biogenesis in the ER. To meet demands encountered by the diverse protein clientele that mature in the ER, this organelle is populated with a cadre of molecular chaperones that prevent protein aggregation, facilitate protein disulfide isomerization, and lower the activation energy barrier of cis-trans prolyl isomerization.