The dispensability of VH-VL pairing and the indispensability of VL domain integrity in the IgG1 secretion process.

Introduction: The CH1 domain of IgG antibodies controls assembly and secretion, mediated by the molecular chaperone BiP via the endoplasmic reticulum protein quality control (ERQC) mechanism. However, it is not clear whether the variable domains are necessary for this process. Methods: Here, we generated IgG1 antibodies in which the V domain (VH and/or VL) was either removed or replaced, and then assessed expression, assembly, and secretion in HEK293 cells. Results: All Ig variants formed a covalent linkage between the Cγ1 and Cκ, were successfully secreted in an assembled form. Replacement of the cognate Vκ with a non-secretory pseudo Vκ (ψVκ) hindered secretion of individual or assembled secretion of neither heavy chains (HCs) nor light chains (LCs). The ψLC (ψVκ-Cκ) exhibited a less folded structure compared to the wild type (wt) LC, as evidenced by enhanced stable binding to the molecular chaperone BiP and susceptibility to proteolytic degradation. Molecular dynamics simulation demonstrated dramatic alterations in overall structure of ψFab (Fd-ψLC) from wt Fab. Discussion: These findings suggest that V domains do not initiate HC:LC assembly and secretion; instead, the critical factor governing IgG assembly and secretion is the CH-CL pairing. Additionally, the structural integrity of the VL domain is crucial for IgG secretion. These data offer valuable insight into the design of bioactive molecules based on an IgG backbone.

Increased breast cancer incidence among nurses in a tertiary university hospital in South Korea.

Background: A series of breast cancer cases were recently reported in a tertiary university hospital in South Korea. Nurses are generally exposed to risk factors for breast cancer such as night shift work, antineoplastic agents, and job strain. However, the epidemiological evidence of excess incidence among nurses remains lacking. This study aims to investigate the excess incidence of breast cancer among nurses in a tertiary university hospital and provide epidemiological evidence of occupational risk factors. Methods: A retrospective cohort was developed using personnel records of female workers in the nursing department who worked from January 2011 to June 2021 in a tertiary university hospital in South Korea. Sick leave records were used to identify cases of breast cancer. The standardized incidence ratio of breast cancer among nurses was compared to the general population. Results: A total of 5,509 nurses were followed up for 30,404 person-years, and 26 breast cancer cases were identified. This study revealed a significantly increased breast cancer incidence among all included nurses, with a standardized incidence ratio of 1.65 (95% confidence interval [CI]: 1.08-2.41), compared to the general population. Workers, who handle antineoplastic agents in their representative department and current and/or former department, had significantly elevated breast cancer standardized incidence ratios of 2.73 (95% CI: 1.008-5.94) and 3.39 (95% CI: 1.46-6.68), respectively. Conclusions: This study provides significant evidence of increased breast cancer risk among nursing staff in a hospital setting, particularly those who handle antineoplastic drugs. Measures that reduce exposure to risk factors should be implemented, especially anticancer drugs, to protect healthcare professionals. Further research at a national level that focuses on healthcare workers is necessary to validate breast cancer incidence and its contributing factors.

Telecommuting-related health outcomes during the COVID-19 pandemic in South Korea: a national population-based cross-sectional study.

BACKGROUND: Telecommuting has expanded greatly during the COVID-19 pandemic. Since the advent of remote working from home, there has been an ongoing controversy about the positive or negative health-related impact of telecommuting. This study aimed to investigate change in the occupational health risk in South Korean workers involved in telecommuting during the pandemic period compared to daily commuters. METHODS: A population-based cross-sectional study of South Korean workers using the secondary data from the 6th Korean Working Conditions Survey (2020-2021) was designed. A total of 12,354 white-collar wage employees were selected as the study sample. Telecommuting, depression, anxiety, insomnia, fatigue, musculoskeletal pain, headache-eye strain, absenteeism, and presenteeism were measured by self-reported data. Multiple logistic regression models, including gender stratification analysis, were used to estimate the adjusted odds ratio (AOR) with a 95% confidence interval (CI) for the health outcomes of telecommuters. RESULTS: Among the study population, 338 males and 318 females were reported to be telecommuters. The entirely adjusted regression model showed a positive association between telecommuting and anxiety (AOR = 2.82; 95% CI, 1.93-4.10), insomnia (AOR = 1.93; 95% CI, 1.27-2.92), fatigue (AOR = 1.76; 95% CI, 1.30-2.37), musculoskeletal pain (AOR = 1,76; 95% CI, 1.33-2.32), headache-eye strain (AOR = 1.94; 95% CI, 1.48-2.54), presenteeism (AOR = 1.66; 95% CI, 1.20-2.28) respectively. Gender difference was identified in that only female telecommuters had a higher risk of depression (AOR = 1.62; 95% CI, 1.04-2.53) and insomnia (AOR = 2.07; 95% CI, 1.26-3.41) than daily commuters in the adjusted model. CONCLUSION: Telecommuting was significantly associated with an increased risk of various health problems among South Korean workers and females were identified as a more vulnerable group. Although further research is required to ascertain the causal relationship, public health intervention should be considered to prevent the negative effects of telecommuting.

A Recombinant Ig Fragment (IgCw-γεκ) Comprising the Cγ1-Cε2-4 and Cκ Domains Is an Alternative Reagent to Human IgE.

Human IgE is useful for immunological assays, such as sensitization of FcεRI-positive cells and IgE measurement. In this study, we report the development of a recombinant Ig fragment, designated IgCw-γεκ, as an alternative reagent to human IgE. IgCw-γεκ (∼130 kDa) comprises two hybrid constant H chain regions (Cγ1-Cε2-4, each ∼53 kDa) and two constant κ L chains (Cκ, each ∼12 kDa) and lacks a V domain. The presence of Cγ1 instead of Cε1 within the H chain increased the production yield and facilitated assembly of the H and L chains. IgCw-γεκ was produced in cultured human embryonic kidney 293F cells, with a yield of ∼27 mg/l. IgCw-γεκ bound to human FcεRIαRs expressed on the surface of rat basophilic leukemia-2H3 cells. A ß-hexosaminidase release assay revealed that the biological activity of IgCw-γεκ was comparable with that of IgE. The IgE concentration measured using IgCw-γεκ as a standard was similar to that measured using IgE as a standard. These results suggest that the IgCw-γεκ molecule retains the basic characteristics of IgE, but does not cross-react with Ags, making it an alternative to the IgE isotype references used in a variety of immunological assays.

The association between non-regular work patterns and insomnia among Korean wage workers: the fifth Korean working condition survey.

BACKGROUND: Non-regular workers are steadily increasing on account of improving corporate productivity. They are classified as non-permanent, part-time, or non-typical workers. Non-regular work has a negative impact on workers' physical and mental health. This study analyzed the relationship between non-permanent, part-time and non-typical work and insomnia among Korean wage workers, and investigated the differences and interactions between different work patterns. METHODS: The Fifth Korean Working Conditions Survey was used in this study. Non-regular work patterns were classified into 7 types: type 1, sole non-permanent; type 2, sole part-time; type 3, sole non-typical; type 4, part-time-non-typical; type 5, non-permanent-non-typical; type 6, non-permanent-part-time; type 7, all inclusive. Insomnia was measured on a scale from "normal sleep" to "insomnia" based on the 3-item Minimal Insomnia Symptom Scale. Multiple logistic regression was used to analyze the association between non-regular work patterns and insomnia among wage workers. RESULTS: After multivariate adjustment, a significantly increased odds ratio (OR) for insomnia was found in types 1, 2, 3, 4, 5, 6, and 7 of non-regular work patterns compared to regular work patterns. After stratification for shift and night work, the OR of the group with shift and night work was higher than that of the group without shift and night work. CONCLUSIONS: Insomnia was significantly associated with non-regular work patterns. This association was prominent in workers with shifts and night work. This finding suggests that proper work patterns may be needed to reduce the risk of insomnia among Korean wage workers and workers who initially had insomnia should consider these results before placement.

A Dual-Connectivity Mobility Link Service for Producer Mobility in the Named Data Networking.

With the exponential growth of Cyber-Physical Systems (CPSs) technologies, the Internet of Things (IoT) infrastructure has evolved from built-in static infrastructure to a flexible structure applicable to various mobile environments. In this Internet of Mobile Things (IoMT) environment, each IoT device could operate simultaneously as a provider and consumer of information, and could provide new services through the exchange of such information. Named Data Networking (NDN), which could request data by content name rather than location (IP address), is suitable for such mobile IoT environments. However, in the current Named Data Networking (NDN) specification, producer mobility is one of the major problems in need of remedy. Previously proposed schemes for producer mobility use an anchor to hide the producer's movement from consumers. As a result, they require a special anchor node and a signaling procedure to track the current locations of contents. A few anchorless schemes have also been proposed, but they still require mobility signaling and all NDN routers on the signaling path must understand the meaning of the signaling. We therefore propose an anchorless producer mobility scheme for the NDN. This scheme uses a dual-connectivity strategy that can be expressed as a soft handover. Whenever a producer changes its NDN Access Router (NAR), the new mobility link service located on the mobile producer's old NDN face repairs the old link so that the connectivity with the pNAR can be maintained for a while. The old NDN face is removed after the new location information on the contents of the producer is disseminated over the NDN network by the Named-data Link State Routing Protocol (NLSR) routing protocol at the nNAR. The new mobility link service decouples connection and transaction to hide the collapse of the link. Therefore, the NDN's mobility procedure could be simplified as the handover is defined as transaction completion as opposed to a breakdown of links. The proposed scheme prevents the routing information from being abruptly outdated due to producer mobility. Our simulation results show seamless handover when the producer changes its default access router.

Antigen-binding affinity and thermostability of chimeric mouse-chicken IgY and mouse-human IgG antibodies with identical variable domains.

Constant (C)-region switching of heavy (H) and/or light (L) chains in antibodies (Abs) can affect their affinity and specificity, as demonstrated using mouse, human, and chimeric mouse-human (MH) Abs. However, the consequences of C-region switching between evolutionarily distinct mammalian and avian Abs remain unknown. To explore C-region switching in mouse-chicken (MC) Abs, we investigated antigen-binding parameters and thermal stability of chimeric MC-6C407 and MC-3D8 IgY Abs compared with parental mouse IgGs and chimeric MH Abs (MH-6C407 IgG and MH-3D8 IgG) bearing identical corresponding variable (V) regions. The two MC-IgYs exhibited differences in antigen-binding parameters and thermal stability from their parental mouse Abs. However, changes were similar to or less than those between chimeric MH Abs and their parental mouse Abs. The results demonstrate that mammalian and avian Abs share compatible V-C region interfaces, which may be conducive for the design and utilization of mammalian-avian chimeric Abs.

Applications of the immunoglobulin Cw fragment (IgCw) composed of the constant regions of heavy and light (CH and CL) chains.

We report the production and application of a recombinant IgCw molecule, which is composed of only the constant domains of the heavy (CH) and light (CL) chains, lacking a variable (V) domain. We produced IgCw, especially human IgCw-γκ (98 kDa), composed of two human Cγ chains (37 kDa each) and two Cκ chains (12 kDa each), using HEK293F cell culture. We found that the yield of IgCw-γκ protein was ∼20 mg/L, which was comparable to that of full-size IgG; it bound to Fcγ receptor-positive cells with a low background noise on Fcγ receptor-negative cells; and IgCw-γκ can be used as a reference for measurement of Ig concentration. Moreover, Cγ and Cκ chains were easily isolated from IgCw-γκ by a single step of affinity chromatography in the presence of a reducing agent. These results demonstrate that the IgCw molecule has the potential to be used for certain in vitro and in vivo applications as an alternative to an irrelevant isotype control IgG, and to be used a favorable antigen for acquiring isotype-specific antibodies by immunizing animals.