Recent methodological advances towards single-cell proteomics

Studying the central dogma at the single-cell level has gained increasing attention to reveal hidden cell lineages and functions that cannot be studied using traditional bulk analyses. Nonetheless, most single-cell studies exploiting genomic and transcriptomic levels fail to address information on proteins that are central to many important biological processes. Single-cell proteomics enables understanding of the functional status of individual cells and is particularly crucial when the specimen is composed of heterogeneous entities of cells. With the growing importance of this field, significant methodological advancements have emerged recently. These include miniaturized and automated sample preparation, multi-omics analyses, and combined analyses of multiple techniques such as mass spectrometry and microscopy. Moreover, artificial intelligence and single-molecule detection technologies have advanced throughput and improved sensitivity limitations, respectively, over conventional methods. In this review, we summarize cutting-edge methodologies for single-cell proteomics and relevant emerging technologies that have been reported in the last 5 years, and provide an outlook on this research field

Current clinical understanding and effectiveness of portopulmonary hypertension treatment

Portopulmonary hypertension (PoPH) is a rare subtype of Group 1 pulmonary arterial hypertension (PAH) with a poor prognosis. According to the most up-to-date definition, PoPH is characterized by a mean pulmonary arterial pressure (PAP) of >20 mmHg at rest, a pulmonary artery wedge pressure of ≤15 mmHg, and a pulmonary vascular resistance (PVR) of >2 Wood units with portal hypertension. Like PAH, PoPH is underpinned by an imbalance in vasoactive substances. Therefore, current guidelines recommend PAH-specific therapies for PoPH treatment; however, descriptions of the actual treatment approaches are inconsistent. Given the small patient population, PoPH is often studied in combination with idiopathic PAH; however, recent evidence suggests important differences between PoPH and idiopathic PAH in terms of hemodynamic parameters, treatment approaches, survival, socioeconomic status, and healthcare utilization. Therefore, large, multi-center registry studies are needed to examine PoPH in isolation while obtaining statistically meaningful results. PoPH has conventionally been excluded from clinical drug trials because of concerns over hepatotoxicity. Nevertheless, newer-generation endothelin receptor antagonists have shown great promise in the treatment of PoPH, reducing PVR, PAP, and World Health Organization functional class without causing hepatotoxicity. The role of liver transplantation as a treatment option for PoPH has also been controversial; however, recent evidence shows that this procedure may be beneficial in this patient population. In the future, given the shortage of liver donors, predictors of a favorable response to liver transplantation should be determined to select the most eligible patients. Collectively, advances in these three areas could help to standardize PoPH treatment in the clinic

Large-scale Filamentary Structure around the Protocluster at Redshift z=3.1

We report the discovery of a large-scale coherent filamentary structure of Lyman alpha emitters in a redshift space at z=3.1. We carried out spectroscopic observations to map the three dimensional structure of the belt-like feature of the Lyman alpha emitters discovered by our previous narrow-band imaging observations centered on the protocluster at z=3.1. The feature was found to consist of at least three physical filaments connecting with each other. The result is in qualitative agreement with the prediction of the 'biased' galaxy-formation theories that galaxies preferentially formed in large-scale filamentary or sheet-like mass overdensities in the early Universe. We also found that the two known giant Lyman alpha emission-line nebulae showing high star-formation activities are located near the intersection of these filaments, which presumably evolves into a massive cluster of galaxies in the local Universe. This may suggest that massive galaxy formation occurs at the characteristic place in the surrounding large-scale structure at high redshift.Comment: 11 pages, 3 figures, accepted for publication in ApJ Letter

GaN-nanopillar-based light-emitting diodes directly grown on multi-crystalline Si substrates

For the first time, light-emitting diodes based on gallium nitride nanopillar crystals were prepared directly on a multi-crystalline silicon substrate, which is widely utilized in low-cost solar cells. Several double-hetero-p–n-junction structures were fabricated, and bright light emission was obtained from the diodes. In addition, white-light emission was observed in another diode. The multi-crystalline Si substrate can be added to a candidate substrate to realize practical, novel, large-area light-emitting devices

A Ly-alpha Emitter with an Extremely Large Rest-frame Equivalent Width of ~900A at z=6.5: A Candidate of Population III-dominated Galaxy?

We have identified a very interesting Ly-alpha emitter, whose Ly-alpha emission line has an extremely large observed equivalent width of EW_0=436^{+422}_{-149}A, which corresponds to an extraordinarily large intrinsic rest-frame equivalent width of EW_0^{int}=872^{+844}_{-298}A after the average intergalactic absorption correction. The object was spectroscopically confirmed to be a real Ly-alpha emitter by its apparent asymmetric Ly-alpha line profile detected at z=6.538. The continuum emission of the object was definitely detected in our deep z'-band image; thus, its EW_0 was reliably determined. Follow-up deep near-infrared spectroscopy revealed emission lines of neither He II lambda1640 as an apparent signature of Population III, nor C IV lambda1549 as a proof of active nucleus. No detection of short-lived He II lambda1640 line is not necessarily inconsistent with the interpretation that the underlying stellar population of the object is dominated by Population III. We found that the observed extremely large EW_0 of the Ly-alpha emission and the upper limit on the EW_0 of the He II lambda1640 emission can be explained by population synthesis models favoring a very young age less than 2-4Myr and massive metal-poor (Z<10^{-5}) or even metal-free stars. The observed large EW_0 of Ly-alpha is hardly explained by Population I/II synthesis models with Z>10^{-3}. However, we cannot conclusively rule out the possibility that this object is composed of a normal stellar population with a clumpy dust distribution, which could enhance the Ly-alpha EW_0, though its significance is still unclear.Comment: 10 pages, 5 figures. Accepted for publication in Ap