Nanoparticles under a few nanometres in size have structures and material functions that differ from the bulk because of their distinct geometrical shapes and strong quantum confinement. These qualities could lead to unique device applications. Our mass spectral analysis of CdSe nanoparticles reveals that (CdSe)(33) and (CdSe)(34) are extremely stable: with a simple solution method, they grow in preference to any other chemical compositions to produce macroscopic quantities. First-principles calculations predict that these are puckered (CdSe)(28)-cages, with four- and six-membered rings based on the highly symmetric octahedral analogues of fullerenes, accommodating either (CdSe)(5) or (CdSe)(6) inside to form a three-dimensional network with essentially heteropolar sp(3)-bonding. This is in accordance with our X-ray and optical analyses. We have found similar mass spectra and atomic structures in CdS, CdTe, ZnS and ZnSe, demonstrating that mass-specified and macroscopically produced nanoparticles, which have been practically limited so far to elemental carbon, can now be extended to a vast variety of compound systems.

DNA is packaged as chromatin in the interphase nucleus. During mitosis, chromatin fibers are highly condensed to form metaphase chromosomes, which ensure equal segregation of replicated chromosomal DNA into the daughter cells. Despite >1 century of research on metaphase chromosomes, information regarding the higher order structure of metaphase chromosomes is limited, and it is still not clear which proteins are involved in further folding of the chromatin fiber into metaphase chromosomes. To obtain a global view of the chromosomal proteins, we performed proteome analyses on three types of isolated human metaphase chromosomes. We first show the results from comparative proteome analyses of two types of isolated human metaphase chromosomes that have been frequently used in biochemical and morphological analyses. 209 proteins were quantitatively identified and classified into six groups on the basis of their known interphase localization. Furthermore, a list of 107 proteins was obtained from the proteome analyses of highly purified metaphase chromosomes, the majority of which are essential for chromosome structure and function. Based on the information obtained on these proteins and on their localizations during mitosis as assessed by immunostaining, we present a four-layer model of metaphase chromosomes. According to this model, the chromosomal proteins have been newly classified into each of four groups: chromosome coating proteins, chromosome peripheral proteins, chromosome structural proteins, and chromosome fibrous proteins. This analysis represents the first compositional view of human metaphase chromosomes and provides a protein framework for future research on this topic.

Significance Dimerization of HIV-1 protease (PR) plays a critical role in the replication of HIV-1. Darunavir (DRV) inhibits not only proteolytic activity but also PR dimerization. The present study shows that PR dimerization process undergoes two steps and that DRV inhibits the first step of PR dimerization by binding to PR monomers in a one-to-one molar ratio. The present study also demonstrates that DRV binds to a transframe precursor PR protein, indicating that DRV’s monomer binding is involved in the Gag-Pol autoprocessing inhibition. To our knowledge, the present report represents the first demonstration of the two-step PR dimerization dynamics and the mechanism of dimerization inhibition by DRV, which should help design further, more potent novel PR inhibitors.

Amyloid β (Aβ) deposition in the brain is an early and invariable feature of Alzheimer’s disease (AD). The Aβ peptides are composed of about 40 amino acids and are generated from amyloid precursor proteins (APP), by β- and γ-secretases. The distribution of individual Aβ peptides in the brains of aged people, and those suffering from AD and cerebral amyloid angiopathy (CAA), is not fully characterized. We employed the matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) to illustrate the spatial distribution of a broad range of Aβ species in human autopsied brains. With technical advancements such as formic acid pretreatment of frozen autopsied brain samples, we have: i) demonstrated that Aβ1–42 and Aβ1–43 were selectively deposited in senile plaques while full-length Aβ peptides such as Aβ1–36, 1–37, 1–38, 1–39, 1–40, and Aβ1–41 were deposited in leptomeningeal blood vessels. ii) Visualized distinct depositions of N-terminal truncated Aβ40 and Aβ42, including pyroglutamate modified at Glu-3 (N3pE), only with IMS for the first time. iii) Demonstrated that one single amino acid alteration at the C-terminus between Aβ1–42 and Aβ1–41 results in profound changes in their distribution pattern. In vitro, this can be attributed to the difference in the self-aggregation ability amongst Aβ1–40, Aβ1–41, and Aβ1–42. These observations were further confirmed with immunohistochemistry (IHC), using the newly developed anti-Aβ1–41 antibody. Here, distinct depositions of truncated and/or modified C- and N-terminal fragments of Aβs in AD and CAA brains with MALDI-IMS were visualized in a spacio-temporal specific manner. Specifically, Aβ1–41 was detected both with MALDI-IMS and IHC suggesting that a single amino acid alteration at the C-terminus of Aβ results in drastic distribution changes. These results suggest that MALDI-IMS could be used as a standard approach in combination with clinical, genetic, and pathological observations in understanding the pathology of AD and CAA.Electronic supplementary materialThe online version of this article (10.1186/s40478-017-0477-x) contains supplementary material, which is available to authorized users.

Proteome analysis by 2-DE and PMF by MALDI-TOF MS was performed on human amnion and amniotic fluid at term. Ninety-two soluble and nineteen membrane proteins were identified from amnion. Thirty-five proteins were identified from amniotic fluid. Calgranulin A and B were found in all patients infected with Ureaplasma urealyticum, but not in any of the patients without infection, indicating that they are potential markers of intrauterine infection. Identity of calgranulin A and B was confirmed by MALDI-TOF/TOF MS. This study represents the first extensive analysis of the human amnion and amniotic fluid proteome at term and demonstrates that 2-DE and MALDI-TOF MS is a useful tool for identifying clinically significant biomarkers of problematic pregnancies.