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Background: Bok is a poorly characterized Bcl-2 protein family member with roles yet to be clearly defined. It is clear, however, that Bok binds strongly to inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), which govern the mobilization of Ca2+ from the endoplasmic reticulum, a signaling pathway required for many cellular processes. Also known is that Bok has a highly conserved phosphorylation site for cAMP-dependent protein kinase at serine-8 (Ser-8). Whether Bok, or phosphorylated Bok, has any direct impact on the Ca2+ mobilizing function of IP3Rs remains to be established. Methods: Bok Ser-8 phosphorylation was characterized using purified proteins, G-protein coupled receptor agonists that increase cAMP levels in intact cells, mass spectrometry, and immunoreactivity changes. Also, using mammalian cells that exclusively or predominately express IP3R1, to which Bok binds strongly, and a fluorescent Ca2+-sensitive dye or a genetically-encoded Ca2+ sensor, we explored how endogenous and exogenous Bok controls the Ca2+ mobilizing function of IP3R1, and whether Bok phosphorylation at Ser-8, or replacement of Ser-8 with a phosphomimetic amino acid, is regulatory. Results: Our results confirm that Ser-8 of Bok is phosphorylated by cAMP-dependent protein kinase, and remarkably that phosphorylation can be detected with Bok specific antibodies. Also, we find that Bok has suppressive effects on IP3R-mediated Ca2+ mobilization in a variety of cell types. Specifically, Bok accelerated the post-maximal decline in G-protein coupled receptor-induced cytosolic Ca2+ concentration, via a mechanism that involves suppression of IP3R-dependent Ca2+ release from the endoplasmic reticulum. These effects were dependent on the Bok-IP3R interaction, as they are only seen with IP3Rs that can bind Bok (e.g., IP3R1). Surprisingly, Bok phosphorylation at Ser-8 weakened the interaction between Bok and IP3R1 and reversed the ability of Bok to suppress IP3R1-mediated Ca2+ mobilization. Conclusions: For the first time, Bok was shown to directly suppress IP3R1 activity, which was reversed by Ser-8 phosphorylation. We hypothesize that this suppression of IP3R1 activity is due to Bok regulation of the conformational changes in IP3R1 that mediate channel opening. This study provides new insights on the role of Bok, its interaction with IP3Rs, and the impact it has on IP3R-mediated Ca2+ mobilization. [ABSTRACT FROM AUTHOR]

One of the problems with the transportation system to tourist locations in the Bandung Regency area is congestion which causes an increase in average daily traffic (LHR) due to the use of private vehicles. If the vehicle's LHR increases, the vehicle speed will be low and the cost of transporting the vehicle to tourist locations will become expensive. This research aims to calculate the BOK for the Bandung Regency tourist area, calculate the BOT for the Bandung Regency tourist area and analyze the influence of the transportation system in the Bandung Regency tourist area. The research method uses quantitative and qualitative research (mix method). From the results of BOK calculations and analysis using the Pacific Consultant International (PCI) method, the total BOK value for working days and holidays for Curug Cinulang is IDR 56,582.00. Tebing Keraton Rp. 79,841.00, and Ranca Upas Rp. 103,366.00. From the results of BOT calculations and analysis using the Pacific Consultant International (PCI) method, the total BOT value for weekdays and holidays for Curug Cinulang is IDR 59,714.00. Tebing Keraton Rp. 50,959.00 and Ranca Upas Rp. 108,137.00. Based on the results of the analysis, It can be seen from the indicators that the obstacles faced in daily activities, especially in traveling, are having to deal with traffic jams which cause low vehicle speeds, wasting a lot of time and fuel on the road, thus disrupting travel activity plans. [ABSTRACT FROM AUTHOR]

This research aims to test and analyze the absolute and conditional convergence of per capita income from 38 districts/cities in East Java with the variables PAD, BOS and BOK during the period 2020 - 2022. According to the Chow, Hausmann test and Lagrange Multiplier, the panel data convergence model estimates using the fixed effect model method. Results show that in the districts/cities and observation period, divergent conditions occurred. Also, conditional variables did not have a significant influence on the growth of per capita income. This condition can occur because capital and technology are distributed unevenly between districts/cities. The implication of this research is to improve the allocation and distribution of the government budget, especially those related to School Operational Assistance (BOS) and Health Operational Assistance (BOK).

The Bcl-2 family controls apoptosis by direct interactions of pro- and anti-apoptotic proteins. The principle mechanism is binding of the BH3 domain of pro-apoptotic proteins to the hydrophobic groove of anti-apoptotic siblings, which is therapeutically exploited by approved BH3-mimetic anti-cancer drugs. Evidence suggests that also the transmembrane domain (TMD) of Bcl-2 proteins can mediate Bcl-2 interactions. We developed a highly-specific split luciferase assay enabling the analysis of TMD interactions of pore-forming apoptosis effectors BAX, BAK, and BOK with anti-apoptotic Bcl-2 proteins in living cells. We confirm homotypic interaction of the BAX-TMD, but also newly identify interaction of the TMD of anti-apoptotic BCL-2 with the TMD of BOK, a peculiar pro-apoptotic Bcl-2 protein. BOK-TMD and BCL-2-TMD interact at the endoplasmic reticulum. Molecular dynamics simulations confirm dynamic BOK-TMD and BCL-2-TMD dimers and stable heterotetramers. Mutation of BCL-2-TMD at predicted key residues abolishes interaction with BOK-TMD. Also, inhibition of BOK-induced apoptosis by BCL-2 depends specifically on their TMDs. Thus, TMDs of Bcl-2 proteins are a relevant interaction interface for apoptosis regulation and provide a novel potential drug target. Synopsis: The Bcl-2 family proteins BCL-2 and BOK interact via their transmembrane domains (TMDs) at the endoplasmic reticulum (ER). The TMD interaction interface is critical for the inhibition of BOK-induced apoptosis. BOK and BCL-2 directly interact via their C-terminal transmembrane domains in the ER membrane. Molecular-dynamics simulations reveal formation of higher order oligomers and mutation studies verify the relevance of predicted key residues in the BCL-2-TMD and BOK-TMD interaction interface. Inhibition of BOK-induced cell death by BCL-2 depends on TMD interaction thus exemplifying functional impact of TMD interaction on apoptosis regulation. The Bcl-2 family proteins BCL-2 and BOK interact via their transmembrane domains (TMDs) at the endoplasmic reticulum. The TMD interaction interface is critical for the inhibition of BOK-induced apoptosis. [ABSTRACT FROM AUTHOR]

Dynamic changes in the endoplasmic reticulum (ER) morphology are central to maintaining cellular homeostasis. Microtubules (MT) facilitate the continuous remodeling of the ER network into sheets and tubules by coordinating with many ER-shaping protein complexes, although how this process is controlled by extracellular signals remains unknown. Here we report that TAK1, a kinase responsive to various growth factors and cytokines including TGF-β and TNF-α, triggers ER tubulation by activating αTAT1, an MT-acetylating enzyme that enhances ER-sliding. We show that this TAK1/αTAT1-dependent ER remodeling promotes cell survival by actively downregulating BOK, an ER membrane-associated proapoptotic effector. While BOK is normally protected from degradation when complexed with IP3R, it is rapidly degraded upon their dissociation during the ER sheets-to-tubules conversion. These findings demonstrate a distinct mechanism of ligand-induced ER remodeling and suggest that the TAK1/αTAT1 pathway may be a key target in ER stress and dysfunction.

The outer mitochondrial membrane is a busy place. One essential activity for cellular survival is the regulation of membrane integrity by the BCL‐2 family of proteins. Another critical facet of the outer mitochondrial membrane is its close approximation with the endoplasmic reticulum. These mitochondrial‐associated membranes (MAMs) occupy a significant fraction of the mitochondrial surface and serve as key signaling hubs for multiple cellular processes. Each of these pathways may be considered as forming their own specialized MAM subtype. Interestingly, like membrane permeabilization, most of these pathways play critical roles in regulating cellular survival and death. Recently, the pro‐apoptotic BCL‐2 family member BOK has been found within MAMs where it plays important roles in their structure and function. This has led to a greater appreciation that multiple BCL‐2 family proteins, which are known to participate in numerous functions throughout the cell, also have roles within MAMs. In this review, we evaluate several MAM subsets, their role in cellular homeostasis, and the contribution of BCL‐2 family members to their functions. [ABSTRACT FROM AUTHOR]

The Chirp Spread Spectrum(CSS) based wireless communication has been widely used in Wireless Sensor Network(WSN). These sensors generally have slow speed, and is becoming more demand for higher data rate. However, due to the low transmission rate of CSS, there are still many problems to be studied. A new modulation method based on the linear chirps is introduced in this paper. Unlike the BOK(Binary Orthogonal Keying) and DM(Direct Modulation) methods, this modulation technique is to implant Doppler frequency shift into the linear chirps. M-ary modulation is realized in a single pulse by this proposed modulation technique. Demodulation is accomplished by calculating the position of the compress pulse peak within the pulse duration, or by using different reference chirp signals in the matching filter. [ABSTRACT FROM AUTHOR]

The article describes the basic principles of the development and architecture of educational and methodological material in the form of a guide for the development of educational programs for training highly qualified professional personnel in cybersecurity (information security). Such guidance in foreign sources is called a curriculum. As in any curriculum, the main content of this manual is the definition of the cybersecurity body of knowledge (CBK) in the form of a multi-level hierarchical structure of didactic units that determine the content of training. In addition, the manual includes the definition of the minimum required amount of knowledge (core of the CBK) for educational programs in cybersecurity, a description of the set of expected characteristics of graduates and learning outcomes, recommendations for practice-oriented training of students, a system of didactic parameters that determine the recommended hourly workload when studying individual elements of the CBK and the level of knowledge transfer in the development of the required skills and other materials. This guide is developed on the basis of the Cybersecurity Skills Model described in the authors' previous article "The Cybersecurity Skills Model 2020". It can serve as a methodological basis for the development of educational programs on cybersecurity at all levels: bachelor's, specialist's, master's. The guide can also be used in the development of continuing education programs, individual curricula and professional self-study programs related to cybersecurity.

Regulation of cell life and death by members of the BCL-2 family of proteins occurs at the mitochondria. Large portions of the mitochondria’s outer membrane are found in tight approximation with the endoplasmic reticulum (ER), known as mitochondria-associated membranes (MAMs) or mitochondria-ER contact sites (MERCs). We recently reported that BOK is present within MAMs where it regulates Ca2+ transfer from the ER to the mitochondria, appropriate MAM components and MERC structure, and apoptosis.

Cerebral ischemia/reperfusion (I/R) can lead to serious brain function impairments. Long noncoding RNA (lncRNA) CCAAT enhancer binding protein a antisense RNA 1 (CEBPA-AS1) was shown to be upregulated in human ischemic stroke. This study investigated the function and mechanism of CEBPA-AS1 in I/R. An oxygen-glucose deprivation/reperfusion (OGD/R) model was used to induce I/R injury in SH-SY5Y cells in vitro. RT-qPCR examined the expression of CEBPA-AS1, microRNA 24-3p (miR-24-3p), and Bcl-2-related ovarian killer (Bok). The cell viability, apoptosis, oxidative stress in OGD/R treated cells were detected using CCK-8, flow cytometry, Western blotting, and enzyme-linked immunosorbent assays. The relationship among genes was tested by RNA pulldown and luciferase reporter assays. We found that OGD/R upregulated CEBPA-AS1 expression in SH-SY5Y cells. Functionally, CEBPA-AS1 depletion ameliorated OGD/R-induced apoptosis and oxidative stress in SH-SY5Y cells by reducing reactive oxygen species production and superoxide dismutase and glutathione. Mechanistic investigations indicated that CEBPA-AS1 acts as a sponge for miR-24-3p, and miR-24-3p binds to BOK. Moreover, miR-24-3p upregulation or BOK downregulation antagonized the protective role of CEBPA-AS1 depletion in SH-SY5Y cells exposed to OGD/R. Overall, downregulation of CEBPA-AS1 exerts protective functions against OGD/R-induced injury by targeting the miR-24-3p/BOK axis. [ABSTRACT FROM AUTHOR]

Summary: Calcium transfer from the endoplasmic reticulum (ER) to mitochondria is a critical contributor to apoptosis. B cell lymphoma 2 (BCL-2) ovarian killer (BOK) localizes to the ER and binds the inositol 1,4,5-trisphosophate receptor (IP3R). Here, we show that BOK is necessary for baseline mitochondrial calcium levels and stimulus-induced calcium transfer from the ER to the mitochondria. Murine embryonic fibroblasts deficient for BOK have decreased proximity of the ER to the mitochondria and altered protein composition of mitochondria-associated membranes (MAMs), which form essential calcium microdomains. Rescue of the ER-mitochondrial juxtaposition with drug-inducible interorganelle linkers reveals a kinetic disruption, which when overcome in Bok−/− cells is still insufficient to rescue thapsigargin-induced calcium transfer and apoptosis. Likewise, a BOK mutant unable to interact with IP3R restores ER-mitochondrial proximity, but not ER-mitochondrial calcium transfer, MAM protein composition, or apoptosis. This work identifies the dynamic coordination of ER-mitochondrial contact by BOK as an important control point for apoptosis.

Myeloid cell leukemia 1 (MCL1) gene amplification occurs in a wide range of human cancers and protein overexpression associates with malignant cell growth and evasion of apoptosis. We recently reported that disrupting the interaction between the transmembrane domains of MCL1 and BCL-2 related ovarian killer (BOK) induces cell death, thereby suggesting a new target site for anti-tumorigenic strategies.

BCL-2–related ovarian killer (BOK) is—despite its identification over 20 years ago—an incompletely understood member of the BCL-2 family. BCL-2 family proteins are best known for their critical role in the regulation of mitochondrial outer membrane permeabilization during the intrinsic apoptotic pathway. Based on sequence and structural similarities to BAX and BAK, BOK is grouped with these “killers” within the effector subgroup of the family. However, the mechanism of how exactly BOK exerts apoptosis is not clear and controversially discussed. Furthermore, and in accordance with reports on several other BCL-2 family members, BOK seems to be involved in the regulation of a variety of other, “apoptosis-independent” cellular functions, including the unfolded protein response, cellular proliferation, metabolism, and autophagy. Of note, compared with other proapoptotic BCL-2 family members, BOK levels are often reduced in cancer by various means, and there is increasing evidence for BOK modulating tumorigenesis. In this review, we summarize and discuss apoptotic- and non–apoptotic-related functions of BOK, its regulation as well as its physiological and pathophysiological roles.

The Bcl-2 protein family comprises both pro- and antiapoptotic members that control the permeabilization of the mitochondrial outer membrane, a crucial step in the modulation of apoptosis. Recent research has demonstrated that the carboxyl-terminal transmembrane domain (TMD) of some Bcl-2 protein family members can modulate apoptosis; however, the transmembrane interactome of the antiapoptotic protein Mcl-1 remains largely unexplored. Here, we demonstrate that the Mcl-1 TMD forms homooligomers in the mitochondrial membrane, competes with full-length Mcl-1 protein with regards to its antiapoptotic function, and induces cell death in a Bok-dependent manner. While the Bok TMD oligomers locate preferentially to the endoplasmic reticulum (ER), heterooligomerization between the TMDs of Mcl-1 and Bok predominantly takes place at the mitochondrial membrane. Strikingly, the coexpression of Mcl-1 and Bok TMDs produces an increase in ER mitochondrial-associated membranes, suggesting an active role of Mcl-1 in the induced mitochondrial targeting of Bok. Finally, the introduction of Mcl-1 TMD somatic mutations detected in cancer patients alters the TMD interaction pattern to provide the Mcl-1 protein with enhanced antiapoptotic activity, thereby highlighting the clinical relevance of Mcl-1 TMD interactions. [ABSTRACT FROM AUTHOR]

Professor Elms' "how to get to" various items mentioned in the proposed BOK Framework could be an overlay on the BOK Framework. Keywords: Model; system; design; environment; terminology; BOK EN Model system design environment terminology BOK 276 278 3 12/17/21 20211201 NES 211201 I read Professor Elms' contribution to the Special Issue (Elms, [4]) several times. The "how to get to" each of the items in the BOK Framework needs developing in the proposed BOK Framework; the BOK Framework was deliberately written without detailed specifics in order to highlight the bones of a BOK. [Extracted from the article]

Cell death is an essential physiological process required for the proper development and function of the human placenta. Although the mouse is a commonly used animal model for development studies, little is known about the extent and distribution of cell death in the mouse placenta throughout development and its physiological relevance. In the present study, we report the results of a systematic and quantitative assessment of cell death patterns in the placentae of two strains of laboratory mice commonly used for developmental studies—ICR and C57Bl/6. TUNEL staining revealed that ICR and C57Bl/6 placentae exhibited similar cell death patterns to those reported in human placentae during pregnancy, with comparatively infrequent death observed during early gestation, which increased and became more organized towards term. Interestingly, when comparing strain differences, increased cell death was observed in almost all regions of the inbred C57Bl/6 placentae compared to the outbred ICR strain. Finally, since Bcl-2 ovarian killer (Bok) has been reported to be a key player in human placental cell death, we examined its expression in murine placentae throughout gestation. Bok protein expression was observed in all placental regions and increased towards term in both strains. The results of this study indicate that although strain-specific differences in placental cell death exist, the overall rates and patterns of cell death during murine placentation parallel those previously described in humans. Thus, the murine placenta is a useful model to investigate molecular pathways involved in cell death signaling during human placentation. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes are clonal hematopoietic stem cell disorders characterized by cytopenia and intramedullary apoptosis. BCL-2 Ovarian Killer (BOK) is a pro-apoptotic member of the BCL-2 family of proteins which, when stabilized from endoplasmic reticulum-associated degradation (ERAD), induces apoptosis in response to ER stress. Although ER stress appropriately activates the unfolded protein response (UPR) in BOK-disrupted cells, the downstream effector signaling that includes ATF4 is defective. We used Nup98-HoxD13 (NHD13) transgenic mice to evaluate the consequences of BOK loss on hematopoiesis and leukemogenesis. Acute myeloid leukemia developed in 36.7% of NHD13 mice with a Bok gene knockout between the age of 8 and 13 months and presented a similar overall survival to the NHD13 mice. The loss of BOK exacerbated anemia in NHD13 mice, and NHD13/BOK-deficient mice exhibited significantly lower hemoglobin, lower mean cell hemoglobin concentration, and higher mean cell volume than NHD13 mice. Hematopoietic progenitor cell assays revealed a decreased amount of erythroid progenitor stem cells (BFU-E) in the bone marrow of NHD13-transgenic/BOK-deficient mice. RT-qPCR analysis demonstrated decreased mean value of ATF4 in the erythroid progenitors of NHD13 and NHD13/BOK-deficient mice. Our results suggest that in addition to induction of apoptosis in response to ER stress, BOK may regulate erythropoiesis when certain erythroid progenitors experience cell stress. [ABSTRACT FROM AUTHOR]

BCL-2 family proteins regulate the mitochondrial apoptotic pathway. BOK, a multidomain BCL-2 family protein, is generally believed to be an adaptor protein similar to BAK and BAX, regulating the mitochondrial permeability transition during apoptosis. Here we report that BOK is a positive regulator of a key enzyme involved in uridine biosynthesis; namely, uridine monophosphate synthetase (UMPS). Our data suggest that BOK expression enhances UMPS activity, cell proliferation, and chemosensitivity. Genetic deletion of Bok results in chemoresistance to 5-fluorouracil (5-FU) in different cell lines and in mice. Conversely, cancer cells and primary tissues that acquire resistance to 5-FU down-regulate BOK expression. Furthermore, we also provide evidence for a role for BOK in nucleotide metabolism and cell cycle regulation. Our results have implications in developing BOK as a biomarker for 5-FU resistance and have the potential for the development of BOK-mimetics for sensitizing 5-FU-resistant cancers. [ABSTRACT FROM AUTHOR]

Regulation of cell life and death by members of the BCL-2 family of proteins occurs at the mitochondria. Large portions of the mitochondria's outer membrane are found in tight approximation with the endoplasmic reticulum (ER), known as mitochondria-associated membranes (MAMs) or mitochondria-ER contact sites (MERCs). We recently reported that BOK is present within MAMs where it regulates Ca2+ transfer from the ER to the mitochondria, appropriate MAM components and MERC structure, and apoptosis. [ABSTRACT FROM AUTHOR]

BOK is an evolutionarily conserved BCL-2 family member that resembles the apoptotic effectors BAK and BAX in sequence and structure. Based on these similarities, BOK has traditionally been classified as a BAX-like pro-apoptotic protein. However, the mechanism of action and cellular functions of BOK remains controversial. While some studies propose that BOK could replace BAK and BAX to elicit apoptosis, others attribute to this protein an indirect way of apoptosis regulation. Adding to the debate, BOK has been associated with a plethora of non-apoptotic functions that makes this protein unpredictable when dictating cell fate. Here, we compile the current knowledge and open questions about this paradoxical protein with a special focus on its structural features as the key aspect to understand BOK biological functions.

Myeloid cell leukemia 1 (MCL1) gene amplification occurs in a wide range of human cancers and protein overexpression associates with malignant cell growth and evasion of apoptosis. We recently reported that disrupting the interaction between the transmembrane domains of MCL1 and BCL-2 related ovarian killer (BOK) induces cell death, thereby suggesting a new target site for anti-tumorigenic strategies. [ABSTRACT FROM AUTHOR]

Many people related to ICA have over the years been engaged in the creation of Cartographic Body of Knowledge (CartoBoK). Central persons as Lynn Usery, Georg Gartner, David Fairbairn and Harold Mollering (Fairbairn, 2018; Moellering, 2019) has been involved in this work in various occasions. There is also a section for Cartography and visualization in the GIS&T Body of Knowledge, established by the University Consortium for Geographic Information Science (GIS&T BoK, 2016). [ABSTRACT FROM AUTHOR]

In Abram Brummett and Erica K. Salter's excellent paper, "Mapping the Moral Terrain of Clinical Deception," they rightly note that it is sometimes ethically appropriate for health care professionals to deceive patients and families. However, they also note that because doing so violates a prima facie duty of honesty, the ethical burden of proof falls upon the deceiver. Hence, they also provide a sophisticated framework for determining whether any given case is warranted. I applaud their overall approach but also critique some of their claims, in particular, their conclusion that lies of commission require greater justification than those of omission and their conflation of the principles of beneficence and nonmaleficence. I also urge them to give greater attention to how power asymmetries should be accounted for and to the impact such deceptive choices might have on the clinician's character. [ABSTRACT FROM AUTHOR]

As the genomic region containing the Bcl-2-related ovarian killer (BOK) locus is frequently deleted in certain human cancers, BOK is hypothesized to have a tumor suppressor function. In the present study, we analyzed primary non-small-cell lung carcinoma (NSCLC) tumors and matched lung tissues from 102 surgically treated patients. We show that BOK protein levels are significantly downregulated in NSCLC tumors as compared to lung tissues ( p < 0.001). In particular, we found BOK downregulation in NSCLC tumors of grades two ( p = 0.004, n = 35) and three ( p = 0.031, n = 39) as well as in tumors with metastases to hilar (pN1) ( p = 0.047, n = 31) and mediastinal/subcarinal lymph nodes (pN2) ( p = 0.021, n = 18) as opposed to grade one tumors ( p = 0.688, n = 7) and tumors without lymph node metastases ( p = 0.112, n = 51). Importantly, in lymph node-positive patients, BOK expression greater than the median value was associated with longer survival ( p = 0.002, Mantel test). Using in vitro approaches, we provide evidence that BOK overexpression is inefficient in inducing apoptosis but that it inhibits TGFβ-induced migration and epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma-derived A549 cells. We have identified epigenetic mechanisms, in particular BOK promoter methylation, as an important means to silence BOK expression in NSCLC cells. Taken together, our data point toward a novel mechanism by which BOK acts as a tumor suppressor in NSCLC by inhibiting EMT. Consequently, the restoration of BOK levels in low-BOK-expressing tumors might favor the overall survival of NSCLC patients. [ABSTRACT FROM AUTHOR]

Neuronal cell death is often triggered by events that involve intracellular increases in Ca 2+ . Under resting conditions, the intracellular Ca 2+ concentration is tightly controlled by a number of extrusion and sequestering mechanisms involving the plasma membrane, mitochondria, and ER. These mechanisms act to prevent a disruption of neuronal ion homeostasis. As these processes require ATP, excessive Ca 2+ overloading may cause energy depletion, mitochondrial dysfunction, and may eventually lead to Ca 2+ -dependent cell death. Excessive Ca 2+ entry though glutamate receptors (excitotoxicity) has been implicated in several neurologic and chronic neurodegenerative diseases, including ischemic stroke, epilepsy, and Alzheimer's disease. Recent evidence has revealed that excitotoxic cell death is regulated by the B-cell lymphoma-2 (Bcl-2) family of proteins. Bcl-2 proteins, comprising of both pro-apoptotic and anti-apoptotic members, have been shown to not only mediate the intrinsic apoptosis pathway by controlling mitochondrial outer membrane (MOM) integrity, but to also control neuronal Ca 2+ homeostasis and energetics. In this review, the role of Bcl-2 family proteins in the regulation of apoptosis, their expression in the central nervous system and how they control Ca 2+ -dependent neuronal injury are summarized. We review the current knowledge on Bcl-2 family proteins in the regulation of mitochondrial function and bioenergetics, including the fusion and fission machinery, and their role in Ca 2+ homeostasis regulation at the mitochondria and ER. Specifically, we discuss how the ‘pro-apoptotic’ Bcl-2 family proteins, Bax and Bok, physiologically expressed in the nervous system, regulate such ‘non-apoptotic/daytime’ functions. [ABSTRACT FROM AUTHOR]

The pro-apoptotic multidomain Bcl-2 proteins Bax and Bak (also known as BAK1) are considered the gatekeepers of the intrinsic pathway of apoptosis by triggering the mitochondrial release of cytochrome c. The role of the third Bax- and Bak-homologous multidomain protein Bok, however, is still unresolved. As cells doubly deficient for Bax and Bak are largely resistant to various apoptotic stimuli, it has been proposed that Bok is either dispensable for apoptosis or that its role is dependent on Bax and Bak. Here, we demonstrate, in several cell systems, that Bok efficiently induces cytochrome c release and apoptosis even in the complete absence of both Bak and Bax. Moreover, modulation of endogenous Bok levels affects the apoptosis response. By RNA interference and targeted deletion of the Bok gene, we demonstrate that Bok can significantly influence the apoptotic response to chemotherapeutic drugs in ovarian carcinoma cells. Hence, our results not only establish Bok as a Bak- and Bax-independent apoptosis inducer, but also suggest a potential impact of Bok expression in ovarian cancer therapy. [ABSTRACT FROM AUTHOR]

Apoptosis plays vital roles in many physiological process and immune response. BOK is one of the central regulators in apoptosis. In this study, a new BOK homolog (Ec-BOK) was cloned and characterized from Orange-spotted grouper, Epinephelus coioides . Ec-BOK encoded a 210 amino acid peptides which shared 97% identity to Stegastes partitus BOK protein, contained four BH domains and one transmembrane region. Ec-BOK widely expressed in all analyzed tissues with the higher expressions in kidney and spleen. Its expression level was up-regulated after SGIV infection in vitro . Further analysis revealed that overexpression of Ec-BOK inhibited viral genes transcriptions and virus replication in fish cell. Our findings suggested that Ec-BOK might play a role in the immune response against virus. [ABSTRACT FROM AUTHOR]

Periodic updates are required to ensure the ASQ Certified Software Quality Engineer (CSQE) program continues to reflect accepted professional practices. An individual receives the CSQE designation as a result of successfully completing the certification exam. In turn, the exam is built on the content described in the current CSQE Body of Knowledge (BoK). This BoK has just undergone its latest revision. This article describes the revision process, starting with a job analysis survey. After survey results were used to modify the BoK, corresponding changes were made to the question bank for the certification exam. Finally, an updated draft exam was produced and evaluated. Specific changes that were made to the BoK are available online and will be discussed in a subsequent article. [ABSTRACT FROM AUTHOR]

Age related decline in reproductive performance in women is well documented and apoptosis has been considered as one of the reasons for the decline of primordial follicle reserve. Recently we observed a decline in the efficiency of DNA repair ability in aged rat primordial follicles as demonstrated by decreased mRNA levels of DNA repair genesBRCA1andH2AX. In the present study, a two-dimensional electrophoresis (2DE) proteomic approach was employed to identify differentially expressed proteins in primordial follicles isolated from ovaries of immature (∼20 days) and aged (∼400–450 days) rats. Using MALDI-TOF/TOF MS, we identified 13 differentially expressed proteins (p < 0.05) which included seven up-regulated and six down-regulated proteins in aged primordial follicles. These proteins are involved in a wide range of biological functions including apoptosis, DNA repair, and the immune system. Interestingly, the differentially expressed proteins such as FIGNL1 (DNA repair) and BOK (apoptotic protein) have not been previously reported in the rat primordial follicles and these proteins can be related to some common features of ovarian aging such as loss of follicle reserve and genome integrity. The quantitative differences of two important proteins BOK and FIGNL1 observed by the proteomic analysis were correlated with the transcript levels, as determined by semi-quantitative RT-PCR. Our results improve the current knowledge about protein factors associated with molecular changes in rat primordial follicles as a function of aging and our understanding of the proteomic processes involved in degenerative changes observed in aging primordial follicles. [ABSTRACT FROM PUBLISHER]

In this study, we have reported a molecular characterization of the first B cell lymphoma-2 (BCL-2) related ovarian killer protein (BOK) from freshwater prawn Macrobrachium rosenbergii ( Mr ). BOK is a novel pro-apoptotic protein of the BCL-2 family that entails in mediating apoptosis to remove cancer cells. A cDNA sequence of Mr BOK was identified from the prawn cDNA library and its full length was obtained by internal sequencing. The coding region of Mr BOK yields a polypeptide of 291 amino acids. The analysis revealed that Mr BOK contains a transmembrane helix at V 261 –L 283 and a putative BCL-2 family domain at V 144 –W 245 . Mr BOK also possessed four putative BCL-2 homology domains including BH1, BH2, BH3 and weak BH4. The BH3 contains 21 binding sites and among them five residues are highly conserved with the aligned BOK proteins. The homology analysis showed that Mr BOK shared maximum similarity with the Caligus rogercresseyi BOK A. The topology of the phylogenetic tree was classified into nine sister groups which includes BOK, BAK, BAX, BAD, BCL-2, BCL-XL, NR13 and MCL members. The BOK protein group further sub-grouped into vertebrate and invertebrate BOK, wherein Mr BOK located within insect monophyletic clad of invertebrate BOK. The secondary structural analysis showed that Mr BOK contains 11 α-helices (52.2%) which are connected over random coils (47.7%). The 3D structure of Mr BOK showed three central helices (α6, α7 and α8) which formed the core of the protein and are flanked on one side by α1, α2 and α3, and on the other side by α4, α5 and α11. Mr BOK mRNA is expressed most abundantly (P < 0.05) in ovary compared to other tissues taken for analysis. Hence ovary was selected to study the possible roles of Mr BOK mRNA regulation upon bacterial ( Aeromonas hydrophila and Vibrio harveyi ) and viral [white spot syndrome virus (WSSV) and M. rosenbergii nodovirus] infection. During bacterial and viral infection, the highest Mr BOK mRNA transcription was varied at different time points. In bacterial infected ovary tissue, the highest mRNA expression was at 24 h post-infection, whereas in viral infection, the expression was highest at 48 h post-infection. Thus we can conclude that Mr BOK functions as an apoptotic protein in intracellular programmed cell-death pathway to counteract the anti-apoptotic proteins released by bacterial and viral pathogens at the time of infection. This is the first study that emphasizes the importance of BOK during bacterial and viral infection in crustacean. [ABSTRACT FROM AUTHOR]

B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) is a BCL-2 family protein with high homology to the multidomain proapoptotic proteins BAX and BAK, yet Bok-/- and even Bax-/-Bok-/- and Bak-/-Bok-/- mice were reported to have no overt phenotype or apoptotic defects in response to a host of classical stress stimuli. These surprising findings were interpreted to reflect functional compensation among the BAX, BAK, and BOK proteins. However, BOK cannot compensate for the severe apoptotic defects of Bax-/- Bak-/- mice despite its widespread expression. Here, we independently developed Bok-/- mice and found that Bok-/- cells are selectively defective in their response to endoplasmic reticulum (ER) stress stimuli, consistent with the predominant subcellular localization of BOK at the ER. Whereas Bok-/- mouse embryonic fibroblasts exposed to thapsigargin, A23187, brefeldin A, DTT, geldanamycin, or bortezomib manifested reduced activation of the mitochondrial apoptotic pathway, the death response to other stimuli such as etoposide, staurosporine, or UV remained fully intact. Multiple organs in Bok-/- mice exhibited resistance to thapsigargin-induced apoptosis in vivo. Although the ER stress agents activated the unfolded protein response, both ATF4 and CHOP activation were diminished in Bok-/- cells and mice. Importantly, BAX and BAK were unable to compensate for the defective apoptotic response to ER stress observed in SV40-transformed and primary Bok-/- cells, and in vivo. These findings support a selective and distinguishing role for BOK in regulating the apoptotic response to ER stress, revealing-to our knowledge-the first bona fide apoptotic defect linked to Bok deletion. [ABSTRACT FROM AUTHOR]

Abstract: Improvements in the spatial resolution of structural and functional MRI are beginning to enable analysis of intracortical structures such as heavily myelinated layers in 3D, a prerequisite for in-vivo parcellation of individual human brains. This parcellation can only be performed precisely if the profiles used in cortical analysis are anatomically meaningful. Profiles are often constructed as traverses that are perpendicular to computed laminae. In this case they are fully determined by these laminae. The aim of this study is to evaluate models for cortical laminae used so far and to establish a new model. Methods to model the laminae used so far include constructing laminae that keep a constant distance to the cortical boundaries, so-called equidistant laminae. Another way is to compute equipotentials between the cortical boundary surfaces with the Laplace equation. The Laplace profiles resulting from the gradients to the equipotentials were often-used because of their nice mathematical properties. However, the equipotentials these Laplacian profiles are constructed from and the equidistant laminae do not follow the anatomical layers observed using high resolution MRI of cadaver brain. To remedy this problem, we introduce a novel equi-volume model that derives from work by Bok (1929). He argued that cortical segments preserve their volume, while layer thickness changes to compensate cortical folding. We incorporate this preservation of volume in our new equi-volume model to generate a three-dimensional well-adapted undistorted coordinate system of the cortex. When defined by this well-adapted coordinate system, cortical depth is anatomically meaningful. We compare isocontours from these cortical depth values to locations of myelinated bands on high-resolution ex-vivo and in-vivo three-dimensional MR images. A similar comparison was performed with equipotentials computed with the Laplace equation and with equidistant isocontours. A quantitative evaluation of the equi-volume model using measured image intensities confirms that it provides a much better fit to observed cortical layering. [Copyright &y& Elsevier]

The Central Institute for Brain Research was founded in Amsterdam in 1908 as part of an international effort to study the nervous system with multiple institutions and various disciplines. The development of research in the past hundred years at the Brain Institute has hardly been documented. We analyze the history of this institute by means of brief portraits of its directors and their main research topics. It appears that each director introduced his own branch of neuroscience into the institute. Initially, mainly comparative neuroanatomical data were collected. Following the Second World War, the multidisciplinary approach slowly developed with research programs on systems neuroscience, neuroendocrinology, and brain disorders. Every new director introduced new approaches to the study of the brain and thus played an important role in keeping brain research in the Netherlands at the international forefront where it has been ever since its foundation in 1908. [ABSTRACT FROM PUBLISHER]

Abstract: In a majority of cases, colorectal cancer is initiated by aberrant activation of the WNT signaling pathway. Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or β-catenin causes constitutively active β-catenin/TCF-mediated transcription, driving the transformation of intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However, the contribution of WNT signaling to this process is not fully understood. We addressed this role by analyzing the rate of epithelial apoptosis in aberrant crypts and adenomas of the ApcMin / + mouse model. In comparison with normal crypts and adenomas, aberrant crypts displayed a dramatically increased rate of apoptotic cell death. Expression profiling of apoptosis-related genes along the crypt-villus axis and in Apc mutant adenomas revealed increased expression of two pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to-surface axis, and of dysplastic crypts, corroborated this expression pattern. Disruption of β-catenin/TCF-4-mediated signaling in the colorectal cancer cell line Ls174T significantly decreased BOK and BAX expression, confirming WNT-dependent regulation in intestinal epithelial cells. Our results suggest a feedback mechanism by which uncontrolled epithelial cell proliferation in the stem cell compartment can be counterbalanced by an increased propensity to undergo cell death. [Copyright &y& Elsevier]

Abstract: Of eight million oocytes formed in fetal ovaries, only 400 are ovulated and the rest are degraded via apoptosis. Studies in rodents suggest an important role for Bok and Bcl-XL in ovarian apoptosis, but their expression patterns and roles in human ovaries are not well known. Protein expression of Bok and Bcl-XL as well as the death pathway effectors TNF and caspase-3 were determined in an important collection of samples consisting of human fetal and adult ovaries. A penetrant expression of Bok, Bcl-XL, TNF and full length and cleaved caspase-3 were characterized in fetal ovaries, with specific patterns in oocytes and pre-granulosa/granulosa cells. Bok and Bcl-XL were detected also in adult ovaries. Lentiviral shRNA delivery demonstrated that loss of Bok markedly reduces vulnerability to apoptosis and, conversely, loss of Bcl-XL increases apoptosis in human granulosa tumour cell line. The results suggest important roles for Bok and Bcl-XL in human ovarian development, follicle maturation and apoptosis. [ABSTRACT FROM AUTHOR]

In this paper I discuss openness and its converse, closeness, in science and society. Openness is an aspiration which is achieved to varying extents in different situations and by different actors in human culture. I identify confidence (here used primarily in the sense self-confidence) and trust as essential conditions for openness to flourish, and integrity as an overarching quality which fosters openness, confidence and trust. The principal example here treated concerns the views and practice of the physicist Niels Bohr, in his science and in his advocacy of openness in the science-related matter of the international control of nuclear weapons. [ABSTRACT FROM AUTHOR]

During the past 10 years, the creation of a Cartographic Body of Knowledge (CartoBoK) has been a recurring issue in ICA. In 2006 the University Consortium for Geographic information Science introduced their GIS&T Body of Knowledge. The collection has later been prepared for the Web environment, and the version of today is from 2016 (GIS&T BoK, 2016). This BoK also includes a section on Cartography and Visualization. The section has however been considered as "not complete" when it comes to Cartography. As Chair of the ICA Commission for Education and Learning, David Fairbairn engaged in the BoK for Cartography work (Fairbairn, 2018). In parallel, the Executive Committee at ICA established a BoK Working Group in the period 2015-2019. This WG was chaired by Lynn Usery and co-chaired by Georg Gartner. Based on an evaluation of existing BoKs in neighbouring domains a comprehensive concept was developed, consisting of a starting list of terms, a strategy to involve the community through ICA Commissions, ICA conference participants and ultimately the crowd, and a concept to maintain the BoK by including consequently standardized meta data and allow for linked data relations to update entries. However, their work did not end up in a common agreement on a Cartographic BoK at the ICC in Tokyo 2019. In 2019, Harold Moellering (Moellering, 2019) did also look into the background for developing CartoBoK, in particular from the Analytical Cartography viewpoint. Since the status for CartoBoK was "mission not completed" in 2019, the current President of ICA wanted a new focus on the establishment of the Body of Knowledge. Accordingly, he formed a new Working Group based on three members of the current Executive Committee. Later this group has been extended, and the current members are the authors of this paper. Since the autumn 2020 this group has, through regularly online meetings, engaged in the CartoBoK work. At the ICA Generally Assembly in Tokyo, 2019, a review and renewal of existing, central definitions within Cartography was requested. In particular the definition of "a map". This task was assigned to the CartoBoK WG. A separate paper dealing with the suggested definitions is proposed for ICC in Florence (Lapaine et al., In review). Another important issue is to establish how to structure the BoK. The WG concluded that "the map" is the most central element, and that other elements within Cartography are somehow connected to the map. We have basic Cartographic elements that are common for most Cartographic work (for example map projections), while other elements are unique for special fields of Cartography. With a view to establish the CartoBok, the WG have studied BoKs for several other sciences. This includes Business Analysis (BABOK, 2015), Surveying (Bethel, 2011; Greenfeld, 2011a; Greenfeld, 2011b; Greenfeld, 2011c; Lathorp, 2011a; Lathorp, 2011b; Paiva, 2011) and Art (Wang, 2000; Stanley, 2006; Wu, 2020). GIS&T BoK (2016) is of course in particular interesting, since it includes Cartography and Visualization as a subset. GIS&T BoK (2016) is also included as a part of the EO4GEO group (Earth Observation for Geoinformation) (EO4GEO BoK, 2018). The EO4GEO group uses "Living Textbook" (Living Textbook, 2021) and a "BoK Visualization and Search tool (BoK Visualization and Search, 2021) "for acquisition and presentation of the BoK. These tools are very intriguing, and similar approaches are considered for the CartoBoK. During the study of other BoKs, the WG concluded that the CartoBoK need to be a dynamic and maintained on a digital platform. It should not be a static document which can be cumbersome to update. It will be natural to use a kind of Web-based platform. The different ICA commissions will play an important role when it comes to the content of CartoBoK. Many Cartographic elements are of common interest for several Commissions, while each of them also can have more specialized contributions for the BoK. As mentioned earlier, CartoBoK needs to be dynamic. Even if much of the content will exist for a long time, new technology and new methods will demand a system for continuous updating and renewal of the BoK. This should be handled by ICA. Maybe we need a permanent Working Group allocated to this task? It is our intention to present the ongoing work in the CartoBoK Working Group at ICC in Florence, to get inputs and acceptance from the Cartographic community for our further work. [ABSTRACT FROM AUTHOR]

Bcl-2-family proteins are central regulators of cell life and death. At least three major classes of Bcl-2-family proteins have been delineated, including proapoptotic proteins that contain several conserved regions of sequence similarity (termed ‘multidomain’). In mammals, the multidomain proteins (MDPs) of the Bcl-2 family include Bax, Bak, and Bok. The founding member of the MDP group of Bcl-2-family proteins was discovered by Stanley Korsmeyer and co-workers, initiating an exciting area of cell death research. The status of current knowledge about the mechanisms and functions of MDPs is reviewed here, and some areas for future research are outlined. Therapeutic opportunities emerging from a growing understanding of MDPs with respect to their three-dimensional structures, biochemical actions, and roles in disease raise hopes that the foundation of basic research laid by Korsmeyer and others will eventually be translated into clinical benefits, leaving a legacy that benefits the world for many decades.Cell Death and Differentiation (2006) 13, 1378–1386. doi:10.1038/sj.cdd.4401975; published online 2 June 2006 [ABSTRACT FROM AUTHOR]

One of the most effective ways to combat different types of cancer is through early diagnosis and administration of effective treatment, followed by efficient monitoring that will allow physicians to detect relapsing disease and treat it at the earliest possible time. Apoptosis, a normal physiological form of cell death, is critically involved in the regulation of cellular homeostasis. Dysregulation of programmed cell death mechanisms plays an important role in the pathogenesis and progression of cancer as well as in the responses of tumours to therapeutic interventions. Many members of the BCL2 (B-cell CLL/lymphoma 2; Bcl-2) family of apoptosis-related genes have been found to be differentially expressed in various malignancies, and some are useful prognostic cancer biomarkers. We have recently cloned a new member of this family, BCL2L12 , which was found to be differentially expressed in many tumours. Most of the BCL2 family genes have been found to play a central regulatory role in apoptosis induction. Results have made it clear that a number of coordinating alterations in the BCL2 family of genes must occur to inhibit apoptosis and provoke carcinogenesis in a wide variety of cancers. However, more research is required to increase our understanding of the extent to which and the mechanisms by which they are involved in cancer development, providing the basis for earlier and more accurate cancer diagnosis, prognosis and therapeutic intervention that targets the apoptosis pathways. In the present review, we describe current knowledge of the function and molecular characteristics of a series of classic but also newly discovered genes of the BCL2 family as well as their implications in cancer development, prognosis and treatment. [ABSTRACT FROM AUTHOR]

The French Oulipo ( Ouvroir de littérature potentielle ) has long experimented with procedural or rule-governed poetics, its members creating elaborate numerical constraints that a given text must follow. Jacques Roubaud and Michel Benabou, for example, collected hundreds of alexandrines, broke them into hemistichs and recombined the latter so as to create a whole set of new poems, the purpose being to show the possibilities of the alexandrine as verse form. Indeed, in his brilliant critical study La Vieillesse d'Alexandre , Jacques Roubaud makes the case for a new 'formal' poetry that by no means uses standard metrics. The poetry of constraint is finally catching on in the English-speaking world, providing an alternative to the self-centred, slack, 'unpoetic' free verse that has become ubiquitous. The cardinal rule of procedural poetics is that the constraint in question is not just a formal device but becomes a thematic property of the poem or fiction. This article discusses recent procedural poetry in English, beginning with the example of Harry Matthews' '35 variations on a theme from Shakespeare', and then focusing on the work of two younger poets, the Canadian Christian Bök and the English poet Caroline Bergvall. Bök's Eunoia is an inverted lipogram, its five sections each built on a single vowel, A, E, I, O, U, and submitting its words to a series of other rules. The long poem demonstrates what sound repetition does and can do in poetry. Bergvall's VIA , a rule-governed sequence based on translations of the first tercet of Dante's Inferno , is another brilliant tour de force . Her more recent 'About face', while not, strictly speaking, a rule-governed composition, uses pun, sound play and elaborate verbal device to create a composition whose sonic artifice stands in sharp opposition to the typical lineated but otherwise quite prosaic verse that is now the norm. [ABSTRACT FROM AUTHOR]

Epithelial cells within the mammary gland undergo apoptosis during weaning. To determine the expression of Bok mRNA (it member of the pro-apoptotic Bcl-2 family) in the mammary gland and its regulation, we examined the expression of the Bok transcript in the mouse mammary gland and HC11 mammary epithelial cells in culture through RT-PCR. The Bok mRNA expression was found in the mammary gland. The expression of the Bok mRNA level was induced through serum starvation and overexpression of Bok induced apoptosis in HC11 cells in culture. These results indicate that the expression of Bok mRNA in the mammary gland is regulated through serum starvation. It also may be related to the mammary involution. [ABSTRACT FROM AUTHOR]

In order to improve anti-multipath interference debility of linear frequency modulation (Chirp) binary orthogonal keying (BOK), this paper proposed an algorithm emploied square law detection and equalization. Square law detection could resist the influence on pulse compression caused by frequency offset and phase offset, to low complexity and enhance robust, its performance reduction was less than 0. 2 dB in the condition of high frequency offset and doppler frequency shift extension. This paper analyzed the equalization model of BOK square law detection, demonstrated the feasibility of the equalization and corroborated the performance of equalization and detection in multipath channel with high frequency offset and doppler frequency shift extension. The simulation results indicate that introducing square law detection and equalization can efficiently improve system performance. [ABSTRACT FROM AUTHOR]

BOK is an evolutionarily conserved BCL-2 family member that resembles the apoptotic effectors BAK and BAX in sequence and structure. Based on these similarities, BOK has traditionally been classified as a BAX-like pro-apoptotic protein. However, the mechanism of action and cellular functions of BOK remains controversial. While some studies propose that BOK could replace BAK and BAX to elicit apoptosis, others attribute to this protein an indirect way of apoptosis regulation. Adding to the debate, BOK has been associated with a plethora of non-apoptotic functions that makes this protein unpredictable when dictating cell fate. Here, we compile the current knowledge and open questions about this paradoxical protein with a special focus on its structural features as the key aspect to understand BOK biological functions. [ABSTRACT FROM AUTHOR]

B-cell lymphoma 2 (Bcl-2) related ovarian killer (BOK) is a member of the Bcl-2 family, which has a similar function to BAX and BAK in the process of apoptosis. However, how BOK activates the intrinsic (mitochondrial) apoptotic pathway remains poorly understood in invertebrates. In this study, Sp BOK identified in mud crab is an important effector responsible for the anti-WSSV (White Spot Syndrome Virus) infection by activating the apoptotic pathway. The Sp BOK gene encoded a 282 amino acid peptides (molecular mass of 29 kD), which contained four distinct Bcl-2 family homology (BH) domains. Sp BOK was widely expressed in all tested tissues and up-regulated after WSSV infection in vivo. The role of Sp BOK on the anti-WSSV response in mud crab was investigated by using the RNAi approach in vivo. Sp BOK exerted a regulatory role in changing the mitochondrial membrane potential (⊿ψm) and activating the caspase signaling and thus induced apoptosis. Moreover, the results showed that WSSV replication in mud crab could be effectively inhibited by Sp BOK. Therefore, the results of this study demonstrated that Sp BOK can inhibit WSSV infection by regulating the intrinsic apoptosis pathway in mud crab. • Sp BOK was significantly up-regulated after WSSV infection in vivo in mud crab. • Sp BOK activates the caspase signaling by reducing the mitochondrial membrane potential (⊿ψm). • Sp BOK inhibits WSSV infection by promoting intrinsic apoptosis in mud crabs. [ABSTRACT FROM AUTHOR]