Two Specific Sulfatide Species Are Dysregulated during Renal Development in a Mouse Model of Alport Syndrome.

Alport syndrome is caused by mutations in collagen IV that alter the morphology of renal glomerular basement membrane. Mutations result in proteinuria, tubulointerstitial fibrosis, and renal failure but the pathogenic mechanisms are not fully understood. Using imaging mass spectrometry, we aimed to determine whether the spatial and/or temporal patterns of renal lipids are perturbed during the development of Alport syndrome in the mouse model.

Transcriptome analysis uncovers Arabidopsis F-BOX STRESS INDUCED 1 as a regulator of jasmonic acid and abscisic acid stress gene expression.

Background: The ubiquitin 26S proteasome system (UPS) selectively degrades cellular proteins, which results in physiological changes to eukaryotic cells. F-box proteins are substrate adaptors within the UPS and are responsible for the diversity of potential protein targets. Plant genomes are enriched in F-box genes, but the vast majority of these have unknown roles.

Decellularization of intact tissue enables MALDI imaging mass spectrometry analysis of the extracellular matrix.

Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is a powerful molecular mapping technology that offers unbiased visualization of the spatial arrangement of biomolecules in tissue. Although there has been a significant increase in the number of applications employing this technology, the extracellular matrix (ECM) has received little attention, likely because ECM proteins are mostly large, insoluble and heavily cross-linked. We have developed a new sample preparation approach to enable MALDI IMS analysis of ECM proteins in tissue.

MALDI imaging mass spectrometry: spatial molecular analysis to enable a new age of discovery.

Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) combines the sensitivity and selectivity of mass spectrometry with spatial analysis to provide a new dimension for histological analyses to provide unbiased visualization of the arrangement of biomolecules in tissue. As such, MALDI IMS has the capability to become a powerful new molecular technology for the biological and clinical sciences. In this review, we briefly describe several applications of MALDI IMS covering a range of molecular weights, from drugs to proteins.

Familial Alzheimer's disease mutations differentially alter amyloid β-protein oligomerization.

Although most cases of Alzheimer's disease (AD) are sporadic, ∼5% of cases are genetic in origin. These cases, known as familial Alzheimer's disease (FAD), are caused by mutations that alter the rate of production or the primary structure of the amyloid β-protein (Aβ). Changes in the primary structure of Aβ alter the peptide's assembly and toxic activity.

Z-Phe-Ala-diazomethylketone (PADK) disrupts and remodels early oligomer states of the Alzheimer disease Aβ42 protein.

The oligomerization of the amyloid-β protein (Aβ) is an important event in Alzheimer disease (AD) pathology. Developing small molecules that disrupt formation of early oligomeric states of Aβ and thereby reduce the effective amount of toxic oligomers is a promising therapeutic strategy for AD. Here, mass spectrometry and ion mobility spectrometry were used to investigate the effects of a small molecule, Z-Phe-Ala-diazomethylketone (PADK), on the Aβ42 form of the protein.

Aβ(39-42) modulates Aβ oligomerization but not fibril formation.

Recently, certain C-terminal fragments (CTFs) of Aβ42 have been shown to be effective inhibitors of Aβ42 toxicity. Here, we examine the interactions between the shortest CTF in the original series, Aβ(39-42), and full-length Aβ. Mass spectrometry results indicate that Aβ(39-42) binds directly to Aβ monomers and to the n = 2, 4, and 6 oligomers.