Serine 58 of 14-3-3ζ Is a molecular switch regulating ASK1 and oxidant stress-induced cell death

Oxidant stress is a ubiquitous stressor with negative impacts on multiple cell types. ASK1 is a central mediator of oxidant injury, but while mechanisms of its inhibition, such as sequestration by 14-3-3 proteins and thioredoxin, have been identified, mechanisms of activation have remained obscure and the signaling pathways regulating this are not clear. Here, we report that phosphorylation of 14-3-3ζ at serine 58 (S58) is dynamically regulated in the cell and that the phosphorylation status of S58 is a critical factor regulating oxidant stress-induced cell death. Phosphorylation of S58 releases ASK1 from 14-3-3ζ, and ASK1 then activates stress-activated protein kinases, leading to cell death. While several members of the mammalian sterile 20 (Mst) family of kinases can phosphorylate S58 when overexpressed, we identify Ste20/oxidant stress response kinase 1 (SOK-1), an Mst family member known to be activated by oxidant stress, as a central endogenous regulator of S58 phosphorylation and thereby of ASK1-mediated cell death. Our findings identify a novel pathway that regulates ASK1 activation and oxidant stress-induced cell death

Turning up by turning over : the change of scenery effect in major league baseball

Purpose: This study examined a “change of scenery” effect on performance in major league baseball (MLB). We also tested this effect for voluntary versus involuntary employee departures, as well as employees returning to a past employer. Design/Methodology/Approach: This study uses publicly available MLB performance data from 2004 to 2015. The data comprise 712 team changes for players following two consecutive years with the same organization. Data were analyzed using MANCOVA to assess the impact of changing teams on player performance. Findings: Results indicate players with declining performance benefited significantly from a change of scenery. Following a team change, these players experienced a significant increase in their performance that remained stable through a subsequent season. The effect was not different for players who changed teams via trade and free agency and was modest for those returning to a past organization. Analysis also showed that players leaving while their performance was improving suffered a subsequent performance drop-off in the new organization. Implications: As the war for talent escalates and employees change jobs more frequently, extending our understanding of how performance can be influenced by work context may provide new insight into organization staffing policies. Originality/Value: Results extend field theory by highlighting how past performance interacts with new work contexts to influence performance. This is one of the few studies evaluating the job change-performance relationship, and perhaps the first to account for the effects of performance trends prior to exit

The Need to Be Apart In an Inclusive Educational Setting

This paper illustrates the need for direct acknowledgement and support of children and faculty of color in inclusive educational settings. Muslin recounts her experiences at many different schools and how each offered a new perspective on diversity. The most profound impacts she has made in her community stem from her work at Bank Street School for Children, where she and her fellow faculty recognized the importance of having separate meetings and focus groups devoted to the concerns of people of color within the institution

Wnt5a induces ROR1 to associate with 14-3-3ζ for enhanced chemotaxis and proliferation of chronic lymphocytic leukemia cells.

Wnt5a can activate Rho GTPases in chronic lymphocytic leukemia (CLL) cells by inducing the recruitment of ARHGEF2 to ROR1. Mass spectrometry on immune precipitates of Wnt5a-activated ROR1 identified 14-3-3ζ, which was confirmed by co-immunoprecipitation. The capacity of Wnt5a to induce ROR1 to complex with 14-3-3ζ could be blocked in CLL cells by treatment with cirmtuzumab, a humanized mAb targeting ROR1. Silencing 14-3-3ζ via small interfering RNA impaired the capacity of Wnt5a to: (1) induce recruitment of ARHGEF2 to ROR1, (2) enhance in vitro exchange activity of ARHGEF2 and (3) induce activation of RhoA and Rac1 in CLL cells. Furthermore, CRISPR/Cas9 deletion of 14-3-3ζ in ROR1-negative CLL cell-line MEC1, and in MEC1 cells transfected to express ROR1 (MEC1-ROR1), demonstrated that 14-3-3ζ was necessary for the growth/engraftment advantage of MEC1-ROR1 over MEC1 cells. We identified a binding motif (RSPS857SAS) in ROR1 for 14-3-3ζ. Site-directed mutagenesis of ROR1 demonstrated that serine-857 was required for the recruitment of 14-3-3ζ and ARHGEF2 to ROR1, and activation of RhoA and Rac1. Collectively, this study reveals that 14-3-3ζ plays a critical role in Wnt5a/ROR1 signaling, leading to enhanced CLL migration and proliferation

Prevalence and Protective Factors Against Depression among Adolescents in Three Southern Border Provinces of Thailand

Depression in adolescents is a significant public health issue because adolescents are the age group that most often engage in self-harm. Thus, it is crucial to study the protective factors against depression that integrate internal and external factors. This study aimed to determine the prevalence and examine the protective factors against depression among adolescents in southern Thailand. This study used a descriptive-predictive research design. A total of 440 high school students served as the study's samples. They were selected using purposive sampling techniques with a multistage sampling procedure. Data were analyzed using ordered logistic regression analysis. The results showed that 66.4% of the sample had depression, with most of the students having mild depression at 46.8%. Seven protective factors were found to prevent depression in adolescents. Adolescents who have healthy family relationships and moderate spiritual well-being, in terms of existential well-being, were 16.28 and 0.73 times less likely to have depression, respectively. Meanwhile, adolescents with low levels of psychological immunity in optimism, low and moderate levels of apperception, lack of belief in the power of wisdom and low support from the community, and low and moderate levels of spiritual and religious well-being were more likely to have depression

The Maltase Involved in Starch Metabolism in Barley Endosperm Is Encoded by a Single Gene

During germination and early seedling growth of barley (Hordeum vulgare), maltase is responsible for the conversion of maltose produced by starch degradation in the endosperm to glucose for seedling growth. Despite the potential relevance of this enzyme for malting and the production of alcoholic beverages, neither the nature nor the role of maltase is fully understood. Although only one gene encoding maltase has been identified with certainty, there is evidence for the existence of other genes and for multiple forms of the enzyme. It has been proposed that maltase may be involved directly in starch granule degradation as well as in maltose hydrolysis. The aim of our work was to discover the nature of maltase in barley endosperm. We used ion exchange chromatography to fractionate maltase activity from endosperm of young seedlings, and we partially purified activity for protein identification. We compared maltase activity in wild-type barley and transgenic lines with reduced expression of the previously-characterised maltase gene Agl97, and we used genomic and transcriptomic information to search for further maltase genes. We show that all of the maltase activity in the barley endosperm can be accounted for by a single gene, Agl97. Multiple forms of the enzyme most likely arise from proteolysis and other post-translational modifications

PENDAFTARAN TANAH WAKAF YANG BERASAL DARI TANAH ULAYAT NAGARI (Studi Kasus Konflik Tanah Wakaf Pondok Pesantren Yayasan Darussalam Nagari Koto Gadang Koto Anau, Kecamatan Lembang Jaya, Kabupaten Solok)

ABSTRAK Permasalahan pendaftaran tanah wakaf yang berasal dari tanah adat, khususnya tanah ulayat masyarakat Minangkabau di Sumatera Barat, menjadi isu pertanahan yang kerap terjadi di Indonesia. Banyak tanah ulayat yang diubah menjadi tanah wakaf tanpa melalui prosedur pendaftaran yang sesuai, sehingga menimbulkan ketidakjelasan status hukum tanah tersebut. Proses perwakafan yang masih dilakukan secara konvensional atau di bawah tangan turut memperumit masalah. Kurangnya pemahaman masyarakat mengenai prosedur pendaftaran tanah wakaf dan keberagaman aturan adat antar nagari akibat sistem "adat salingka nagari" turut menjadi hambatan. Salah satu kasus nyata terjadi pada tahun 2022 terkait tanah wakaf Pondok Pesantren Yayasan Pendidikan Darussalam di Nagari Koto Anau, Kecamatan Lembang Jaya, Kabupaten Solok. Rumusan masalah dalam penelitian ini adalah: 1. Bagaimana proses perwakafan tanah yang berasal dari tanah ulayat nagari milik pesantren Yayasan Darussalam Nagari Koto Gadang Koto Anau, Kecamatan. Lembang Jaya, Kabupaten Solok? 2. Apa saja hambatan/kendala dalam pendaftaran tanah wakaf pesantren Yayasan Darussalam Nagari Koto Gadang Koto Anau, Kecamatan. Lembang Jaya, Kabupaten Solok dan bagaimana solusi/upaya penyelesaiannya? 3. Bagaimana akibat hukum dan dampak yang terjadi dalam pendaftaran tanah wakaf pesantren Yayasan Darussalam Nagari Koto Gadang Koto Anau, Kecamatan. Lembang Jaya, Kabupaten Solok ? Jenis penelitian yang digunakan adalah yuridis-empiris (sosiologis), dengan teknik pengumpulan data melalui wawancara dan studi dokumen. Hasil penelitian ini adalah: 1. Proses perwakafan tanah yang berasal dari tanah ulayat nagari untuk pembangunan pesantren Yayasan Darussalam Nagari Koto Gadang Koto Anau, Kecamatan. Lembang Jaya, Kabupaten Solok 2. Hambatan/kendala dalam pendaftaran tanah wakaf pesantren Yayasan Darussalam Nagari Koto Gadang Koto Anau, Kecamatan. Lembang Jaya, Kabupaten Solok dan solusi/upaya penyelesaiannya 3. Akibat hukum dan dampak yang terjadi dalam pendaftaran tanah wakaf pesantren Yayasan Darussalam Nagari Koto Gadang Koto Anau, Kecamatan. Lembang Jaya, Kabupaten Solok. Kata Kunci: Pendaftaran Tanah, Tanah Ulayat, Tanah Waka

Quantification of Osmolytes in the Sargasso Sea Surface Layer Water Column

Oceanic carbon cycling plays a major role in determining global atmospheric CO₂. A better understanding of dissolved organic matter and its constituents in the water column and how it affects marine carbon cycling is sought after. This study successfully measured osmolytes, low molecular zwitterionic compounds derived from amino acids, in depth profiles from the surface to 300 meters in the Sargasso Sea. Dimethylsulfionopropionate (DMSP), glycine betaine, and TMAo are three osmolytes that have been extensively studied. This study identified seven additional osmolytes in seawater for the first time: alanine betaine, propionobetaine, trigonelline, L-proline betaine, betonicine, butyrobetaine, and L-carnitine. We found that these compounds reached a maximum at different depths in the water column. Osmolyte concentrations were in the picomolar (pM) range, and fluctuated depending on time of day, suggesting a relationship to photosynthetic activity. Total osmolytes reached a maximum between 250 and 400 pM at the deep chlorophyll maximum at 80 to 120 meters below surface waters during all sampling times. In addition to these environmental measurements, experiments with cultured photosynthetic organisms were used to investigate the production of osmolytes in extracellular organic matter released by cells. These experiments yielded evidence of the production in culture of many of the osmolytes we had detected in seawate

Chimeric 14-3-3 proteins for unraveling interactions with intrinsically disordered partners

In eukaryotes, several "hub" proteins integrate signals from different interacting partners that bind through intrinsically disordered regions. The 14-3-3 protein hub, which plays wide-ranging roles in cellular processes, has been linked to numerous human disorders and is a promising target for therapeutic intervention. Partner proteins usually bind via insertion of a phosphopeptide into an amphipathic groove of 14-3-3. Structural plasticity in the groove generates promiscuity allowing accommodation of hundreds of different partners. So far, accurate structural information has been derived for only a few 14-3-3 complexes with phosphopeptide-containing proteins and a variety of complexes with short synthetic peptides. To further advance structural studies, here we propose a novel approach based on fusing 14-3-3 proteins with the target partner peptide sequences. Such chimeric proteins are easy to design, express, purify and crystallize. Peptide attachment to the C terminus of 14-3-3 via an optimal linker allows its phosphorylation by protein kinase A during bacterial co-expression and subsequent binding at the amphipathic groove. Crystal structures of 14-3-3 chimeras with three different peptides provide detailed structural information on peptide-14-3-3 interactions. This simple but powerful approach, employing chimeric proteins, can reinvigorate studies of 14-3-3/phosphoprotein assemblies, including those with challenging low-affinity partners, and may facilitate the design of novel biosensors