The expansion of COVID-19 has put Essential Workers in a difficult position. This is because recent public service reforms have excessively led to a reduction in staff, the outsourcing of ...implementing departments and casualization of staff. One of the reasons behind the excessive reforms is the difficulty in evaluating the work performance of street-level bureaucracies working on the front lines of public services. Because of this difficulty, the reform sought to “take them out”. However, the Corona disaster revealed that the recent reforms turned out to be the cause of the problems that hindered the proper implementation of public services and had a negative impact on the residents who were the recipients of the services. In the post-Corona era, it is important to focus on the “workers” who are responsible for public services and to try to improve public services not only from the perspective of policy but also from the perspective of management, such as institutions and resources. We need to approach the work performance of street-level bureaucracies, who are the nexus of policy and management, from the perspective of administrative management, including personnel evaluation, and have a broad discussion about management and ensuring accountability and build a system for meta-evaluation.
The Japanese government will amend the Local Public Service Act and the Local Autonomy Law on April 1, 2020. In this revision, the local government will reconfirm the appointment system of ...part-time staff, adjust the number of posts and types, apply work regulations, and improve the allowance and salary. However, because the government’s control over local governments and the discretion of local governments are ambiguous, this amendment will create new problems. Also, because local governments are short of financial resources, part-time staff may be at risk of reducing post-employment ‘yatoi-dome’, not re-hiring. Full-time staff will increase the burden on personnel evaluation subjects, which will have an adverse effect on “reform of workers”. Therefore, before the government changes the civil servant system, it is necessary to evaluate the new personnel policy in advance, carefully assessing necessity and effectiveness.
In Japanese public administration, the word “efficiency” has historically been translated as “noritsu”. However, in recent years it is now often generally translated as “koritsu”. This change was ...effected by the vogue of New Public Management. Although both “noritsu” and “koritsu” are equivalents of the term “efficiency”, people are not aware that “koritsu” is a new concept and is used as a keyword of the administrative reform in Japan. “Efficiency” itself is not integrally defined in each discipline. For example, in the history of public administration, the concept varies by the times was praised and was criticized. Thus, regardless of whether “noritsu” or “koritsu” is used, if people who are concerned with “public” as well as statesmen and civil servants use it as an evaluation standard for policy, programs and projects, it is essential for them to define the concept clearly and discuss its merit and deficiencies in advance.
A common pathological hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis, is cytoplasmic mislocalization and aggregation of nuclear RNA-binding protein TDP-43. ...Perry disease, which displays inherited atypical parkinsonism, is a type of TDP-43 proteinopathy. The causative gene
encodes the largest subunit of the dynactin complex. Dynactin associates with the microtubule-based motor cytoplasmic dynein and is required for dynein-mediated long-distance retrograde transport. Perry disease-linked missense mutations (e.g., p.G71A) reside within the CAP-Gly domain and impair the microtubule-binding abilities of DCTN1. However, molecular mechanisms by which such
mutations cause TDP-43 proteinopathy remain unclear. We found that DCTN1 bound to TDP-43. Biochemical analysis using a panel of truncated mutants revealed that the DCTN1 CAP-Gly-basic supradomain, dynactin domain, and C-terminal region interacted with TDP-43, preferentially through its C-terminal region. Remarkably, the p.G71A mutation affected the TDP-43-interacting ability of DCTN1. Overexpression of DCTN1
, the dynactin-domain fragment, or C-terminal fragment, but not the CAP-Gly-basic fragment, induced cytoplasmic mislocalization and aggregation of TDP-43, suggesting functional modularity among TDP-43-interacting domains of DCTN1. We thus identified DCTN1 as a new player in TDP-43 cytoplasmic-nuclear transport, and showed that dysregulation of DCTN1-TDP-43 interactions triggers mislocalization and aggregation of TDP-43, thus providing insights into the pathological mechanisms of Perry disease and other TDP-43 proteinopathies.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
With technological applications, especially in genetic testing, new diseases have been discovered and new disease concepts have been proposed in recent years; however, the pathogenesis and treatment ...of these rare diseases are not as well established as those of common diseases. To demonstrate the importance of rare disease research, in this paper we focus on our research topic, Perry disease (Perry syndrome). Perry disease is a rare autosomal dominant neurodegenerative disorder clinically characterized by parkinsonism, depression/apathy, weight loss, and respiratory symptoms including central hypoventilation and central sleep apnea. The pathological classification of Perry disease falls under TAR DNA-binding protein 43 (TDP-43) proteinopathies. Patients with Perry disease exhibit
mutations, which is the causative gene for the disease; they also show relatively uniform pathological and clinical features. This review summarizes recent findings regarding Perry disease from both basic and clinical perspectives. In addition, we describe technological innovations and outline future challenges and treatment prospects. We discuss the expansion of research from rare diseases to common diseases and the importance of collaboration between clinicians and researchers. Here, we highlight the importance of researching rare diseases as it contributes to a deeper understanding of more common diseases, thereby opening up new avenues for scientific exploration.
Hypertension is an important target for drug discovery. We have focused on the with‐no‐lysine kinase (WNK)‐oxidative stress‐responsive 1 (OSR1) and STE20/SPS1‐related proline‐alanine‐rich protein ...kinase (SPAK)‐NaCl cotransporter (NCC) signal cascade as a potential target, and we previously developed a screening system for inhibitors of WNK‐OSR1/SPAK‐NCC signaling. Herein we used this system to examine the structure‐activity relationship (SAR) of salicylanilide derivatives as SPAK kinase inhibitors. Structural design and development based on our previous hit compound, aryloxybenzanilide derivative 2, and the veterinary anthelmintic closantel (3) led to the discovery of compound 10 a as a potent SPAK inhibitor with reduced toxicity. Compound 10 a decreased the phosphorylation level of NCC in mouse kidney in vivo, and appears to be a promising lead compound for a new class of antihypertensive drugs.
We developed novel salicylanilide derivative 10 a as a potent SPAK inhibitor with an improved activity‐toxicity profile. Compound 10 a reduced the phosphorylation level of NCC in mouse kidney in vivo. Compound 10 a appears to be a promising candidate for a new class of antihypertensive drugs.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
PDF
