Transitions to employment of young people in Indonesia

The aim of this research is to examine transition pathways to employment of young Indonesian men and women between 1997 and 2014. Longitudinal Indonesian Family Life Survey (IFLS) data are used to investigate these pathways among cohorts of young people aged 15-29 years as at 1997 in the context of demographic changes. Although Indonesia has the largest economy and youth population in the Southeast Asian region, the country exhibits high youth unemployment. This research provides important insights into youth employment for both men and women, examining their transition patterns and life course experiences. The results of this research show that educated men with high school or higher qualifications steadily moved into service sector jobs, while men with junior high school and lower educational attainment faced more fluctuations. Women experienced a range of transition pathways but mainly fall into four transition patterns. Women with tertiary education continued to work without much interruption due to marriage, while those with less than tertiary education usually stopped working. The results of estimating women's working life expectancy show that tertiary educated women had the longest lifetime working durations. Working women with junior high school and less educational attainment had the shortest working life expectancies despite their early entry into the labour force. These findings support the human capital theory that education has a stronger influence on work expectancy than previous work experience. Life course theory provides a useful framework to cover many factors involved in the young people's pathways. This research contributes to understanding the employment pathways for men and women. Providing more support in occupational skill development for women with less than high school is recommended so that they can become more productive workers for the benefit of the country

Structure of MSPL–inhibitor complex

Infection of certain influenza viruses is triggered when its HA is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, whereas the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R↓ sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal α-helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19

Polyphenols prevent clinorotation-induced expression of atrogenes in mouse C2C12 skeletal myotubes

Oxidative stress is a key factor in stimulating the expression of atrogenes, which are muscle atrophy-related ubiquitin ligases, in skeletal muscle, and it induces muscle atrophy during unloading. However, the effects of antioxidative nutrients on atrogene expression have not been demonstrated. We report on the inhibitory effects of polyphenols, such as epicatechin (EC), epicatechin gallate (ECg) and epigallocatechin gallate (EGCg) and quercetin, on atrogene expression up-regulated by three dimensional (3D)-clinorotation or glucocorticoid. These treatments markedly elevated the expression of atrogenes, including atrogin-1 and MuRF-1, in mouse C2C12 myoblasts and myotubes. Interestingly, EC, ECg, EGCg and quercetin significantly decreased the expression of atrogin-1 and MuRF-1 up-regulated by 3D-clinorotation, whereas they hardly affected atrogene expression induced by dexamethasone. ERK signaling is a well known MAPK pathway to mediate oxidative stress. Therefore, we also investigated the effect of these polyphenols on phosphorylation of ERK in C2C12 myotubes. As expected, EC, ECg, EGCg, and quercetin significantly suppressed phosphorylation of ERK, corresponding to the up-regulation of atrogenes induced by 3D-clinorotation. These results suggest that antioxidative nutrients, such as catechins and quercetin, suppress atrogene expression in skeletal muscle cells, possibly through the inhibition of ERK signaling. Thus, catechins and quercetin may prevent unloading-mediated muscle atrophy

ROS induced Cbl-b expression in rat L6 cells

Unloading-mediated muscle atrophy is associated with increased reactive oxygen species (ROS) production. We previously demonstrated that elevated ubiquitin ligase casitas B-lineage lymphoma-b (Cbl-b) resulted in the loss of muscle volume (Nakao R, Hirasaka K, Goto J, Ishidoh K, Yamada C, Ohno A, Okumura Y, Nonaka I, Yasutomo K, Baldwin KM, Kominami E, Higashibata A, Nagano K, Tanaka K, Yasui N, Mills EM, Takeda S, Nikawa T. Mol Cell Biol 29: 4798–4811, 2009). However, the pathological role of ROS production associated with unloading-mediated muscle atrophy still remains unknown. Here, we showed that the ROS-mediated signal transduction caused by microgravity or its simulation contributes to Cbl-b expression. In L6 myotubes, the assessment of redox status revealed that oxidized glutathione was increased under microgravity conditions, and simulated microgravity caused a burst of ROS, implicating ROS as a critical upstream mediator linking to downstream atrophic signaling. ROS generation activated the ERK1/2 early-growth response protein (Egr)1/2-Cbl-b signaling pathway, an established contributing pathway to muscle volume loss. Interestingly, antioxidant treatments such as N-acetylcysteine and TEMPOL, but not catalase, blocked the clinorotation-mediated activation of ERK1/2. The increased ROS induced transcriptional activity of Egr1 and/or Egr2 to stimulate Cbl-b expression through the ERK1/2 pathway in L6 myoblasts, since treatment with Egr1/2 siRNA and an ERK1/2 inhibitor significantly suppressed clinorotation-induced Cbl-b and Egr expression, respectively. Promoter and gel mobility shift assays revealed that Cbl-b was upregulated via an Egr consensus oxidative responsive element at −110 to −60 bp of the Cbl-b promoter. Together, this indicates that under microgravity conditions, elevated ROS may be a crucial mechanotransducer in skeletal muscle cells, regulating muscle mass through Cbl-b expression activated by the ERK-Egr signaling pathway

Halo ellipticity of GAMA galaxy groups from KiDS weak lensing

We constrain the average halo ellipticity of ~2 600 galaxy groups from the Galaxy And Mass Assembly (GAMA) survey, using the weak gravitational lensing signal measured from the overlapping Kilo Degree Survey (KiDS). To do so, we quantify the azimuthal dependence of the stacked lensing signal around seven different proxies for the orientation of the dark matter distribution, as it is a priori unknown which one traces the orientation best. On small scales, the major axis of the brightest group/cluster member (BCG) provides the best proxy, leading to a clear detection of an anisotropic signal. In order to relate that to a halo ellipticity, we have to adopt a model density profile. We derive new expressions for the quadrupole moments of the shear field given an elliptical model surface mass density profile. Modeling the signal with an elliptical Navarro-Frenk-White (NFW) profile on scales < 250 kpc, which roughly corresponds to half the virial radius, and assuming that the BCG is perfectly aligned with the dark matter, we find an average halo ellipticity of e_h=0.38 +/- 0.12. This agrees well with results from cold-dark-matter-only simulations, which typically report values of e_h ~ 0.3. On larger scales, the lensing signal around the BCGs does not trace the dark matter distribution well, and the distribution of group satellites provides a better proxy for the halo's orientation instead, leading to a 3--4 sigma detection of a non-zero halo ellipticity at scales between 250 kpc and 750 kpc. Our results suggest that the distribution of stars enclosed within a certain radius forms a good proxy for the orientation of the dark matter within that radius, which has also been observed in hydrodynamical simulations

Joint Observation of the Galactic Center with MAGIC and CTA-LST-1

MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes (IACTs), designed to detect very-high-energy gamma rays, and is operating in stereoscopic mode since 2009 at the Observatorio del Roque de Los Muchachos in La Palma, Spain. In 2018, the prototype IACT of the Large-Sized Telescope (LST-1) for the Cherenkov Telescope Array, a next-generation ground-based gamma-ray observatory, was inaugurated at the same site, at a distance of approximately 100 meters from the MAGIC telescopes. Using joint observations between MAGIC and LST-1, we developed a dedicated analysis pipeline and established the threefold telescope system via software, achieving the highest sensitivity in the northern hemisphere. Based on this enhanced performance, MAGIC and LST-1 have been jointly and regularly observing the Galactic Center, a region of paramount importance and complexity for IACTs. In particular, the gamma-ray emission from the dynamical center of the Milky Way is under debate. Although previous measurements suggested that a supermassive black hole Sagittarius A* plays a primary role, its radiation mechanism remains unclear, mainly due to limited angular resolution and sensitivity. The enhanced sensitivity in our novel approach is thus expected to provide new insights into the question. We here present the current status of the data analysis for the Galactic Center joint MAGIC and LST-1 observations