Native proteomics by capillary zone electrophoresis-mass spectrometry.

Native proteomics aims to measure endogenous proteoforms and protein complexes under a near physiological condition using native mass spectrometry (nMS) coupled with liquid-phase separation techniques. Native proteomics should provide the most accurate bird's-eye view of proteome dynamics within cells, which is fundamental for understanding almost all biological processes. nMS has been widely employed to characterize well-purified protein complexes. However, there are only very few trials of utilizing nMS to measure proteoforms and protein complexes in a complex sample (i.e., a whole cell lysate), and those studies are either too time and labor-consuming or only able to detect small proteoforms or protein complexes. Here, we pioneer the native proteomics measurement of large proteoforms or protein complexes up to 400 kDa from a complex proteome via online coupling of native capillary zone electrophoresis (nCZE) to an ultra-high mass range Orbitrap mass spectrometer (UHMR). The nCZE-MS technique enabled the measurement of a 115-kDa standard protein complex while consuming only about 100 pg of protein material, indicating the extremely high sensitivity of the technique. nCZE-MS analysis of an E . coli cell lysate detected 76 and 21 proteoforms or protein complexes in a mass range of 30-400 kDa and over 110 kDa, respectively, in a single run while consuming only 50-ng protein material. The mass distribution of detected proteoforms or protein complexes agreed well with that from mass photometry measurement. This work represents a technical breakthrough of native proteomics for measuring complex proteomes, suggesting that nCZE-MS might be developed as a central technique for native proteomics.

Structures and Electron Affinities of Aluminum Hydride Clusters AlnH (n = 3-13).

Low-energy structures and electron affinities (EAs) for aluminum hydride clusters AlnH (n = 3-13) have been calculated using ab initio and density functional calculations. Geometries were optimized at the PBE0/def-2-TZVPP level of theory, which has been shown to match the currently accepted lowest-energy structures for the all-aluminum clusters Aln and their anions. Neutral hydride clusters with n = 4, 7, and 9-12 are predicted to adopt terminal structures with the hydrogen atom bound to only one aluminum atom and with only minor alterations of the aluminum atom arrangement from that of the all-aluminum cluster. Clusters with n = 3 and 13 are predicted to adopt "face-centered" geometries, and the n = 6 cluster is predicted to prefer an isomer with the hydrogen atom bridging two aluminum atoms, also with little or no distortion to the aluminum atom arrangement from the all-aluminum cluster. Addition of a hydrogen atom to clusters with n = 5 and 8 is predicted to distort the aluminum atom arrangement significantly from that of the corresponding all-aluminum cluster. In the anionic clusters, terminal clusters are preferred for all cluster sizes except for n = 6 that prefers a face-centered arrangement. Minor distortions in the aluminum scaffolding for Al11 and Al12 were found, while all other anionic clusters adopt structures with little or no deviation in the aluminum atom arrangement from the corresponding all-aluminum cluster. Raw adiabatic electron affinities were computed using CCSD(T)/aug-cc-pVTZ single-point energies for the anionic and neutral hydride clusters at their respective DFT geometries. Isodesmic electron affinities for the hydride clusters were computed relative to their all-aluminum counterparts and show an even-odd alternation with cluster size. Derived EAs alternate in magnitude between even- and odd-numbered clusters, with the even-numbered clusters having relatively larger EAs.

Use of placebo in clinical trials in COVID-19 pandemic times: considerations on pros, cons, challenges and limitations.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has placed tremendous strain on health systems throughout the world. This has led to many clinical trials being launched in order to try to find ways to combat the disease. The unprecedented nature of the pandemic has been reflected in the methods used in some of these trials. Placebo-controlled randomized trials are considered the gold-standard, however, there are inherent challenges in the use of placebo, especially during COVID-19. We herein review the pros, cons, challenges and limitations of using placebo in clinical trials investigating treatments for COVID-19. We also discuss the importance of viewing research critically, examining the potential impact of placebo use or lack thereof, on blinding and possible biases. This becomes important as we assess the responses to the pandemic in preparation for a future pandemic. Although placebo-controlled clinical trials are the gold standard for clinical research, they may not be practically or ethically feasible during a pandemic. Choices accomplished to design many COVID-19 trials might reflect the unprecedently trying environment in which they were made. However, critical evaluation of the methodology and practice of scientific research remains a crucial part of the scientific process. Even when conducted as randomized double-blind studies, residual biases may exist and interfere with the study conduct and interpretation of the data. A critical review of all data remains essential to thoroughly assess the impact of a research study.

Parents' professional sources of advice regarding child discipline and their use of corporal punishment.

Parents (n = 500) were surveyed about which professional groups they were most likely to seek and follow advice from regarding child discipline as well as their use of corporal punishment (CP). Nearly half of the parents reported that they were most likely to seek child discipline advice from pediatricians (48%), followed by religious leaders (21%) and mental health professionals (18%). Parents who sought advice from religious leaders (vs pediatricians) had nearly 4 times the odds of reporting use of CP. Parents reported that they were more likely to follow the advice of pediatricians than any other professional; however, black parents were as likely to follow the advice of religious leaders as that of pediatricians. Pediatricians play a central role in advising parents about child discipline. Efforts to engage pediatricians in providing violence prevention counseling should continue. Increased efforts are needed to engage other professionals, especially religious leaders, in providing such advice to parents.