Dampak Penggunaan Alasan Penetapan Skor mengenai Kriteria Kinerja Subjektif dan Aktivitas Grup terhadap Penilaian Kinerja Subjektif dalam Upaya Mengurangi Bias Kemurahan Hati (Leniency)

Topik penelitian ini dipilih untuk menguji apakah bias kemurahan hati (leniency) dapat berkurang melalui adanya pertimbangan penetapan alasan skor dan penggunaan aktivitas penilai. Dalam penelitian ini, peneliti menggunakan metode eksperimen yang diikuti oleh 61 mahasiswa S1 sebagai subjek. Hasil penelitian ini ditemukan bahwa dengan menggunakan alasan penetapan skor dalam melakukan penilaian kinerja mampu mengurangi bias kemurahan hati. Namun, peneliti juga menemukan bahwa aktivitas penilai baik yang dilakukan secara individu maupun kelompok tidak berpengaruh terhadap keakuratan dalam melakukan penilaian. Peneliti juga menemukan bahwa antara penilai grup dan dengan memberikan alasan tidak berpengaruh pada penilaian kinerja manajer. Selain itu, berkenaan dengan asumsi umum mengenai leniency, peneliti menemukan bahwa pemberian nilai kinerja yang tinggi disebabkan oleh sikap altruistik yang dimiliki oleh seseorang. Dengan demikian, dari penelitian eksperimen yang telah peneliti lakukan, peneliti memberikan saran untuk mendapatkan penilaian kinerja yang akurat, bagi perusahaan dalam melakukan suatu penilaian perlu menyertakan alasan melakukan penilaian. Hal ini perlu dilakukan supaya dalam melakukan penilaian, penilai akan mempertimbangkan kinerja manajer yang akan dinilai dengan lebih baik

Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D

Mutations in the N-myc downstream-regulated gene 1 (NDRG1) cause degenerative polyneuropathy in ways that are poorly understood. We have investigated Alaskan Malamute dogs with neuropathy caused by a missense mutation in NDRG1. In affected animals, nerve levels of NDRG1 protein were reduced by more than 70% (p < 0.03). Nerve fibers were thinly myelinated, loss of large myelinated fibers was pronounced and teased fiber preparations showed both demyelination and remyelination. Inclusions of filamentous material containing actin were present in adaxonal Schwann cell cytoplasm and Schmidt-Lanterman clefts. This condition strongly resembles the human Charcot-MarieTooth type 4D. However, the focally folded myelin with adaxonal infoldings segregating the axon found in this study are ultrastructural changes not described in the human disease. Furthermore, lipidomic analysis revealed a profound loss of peripheral nerve lipids. Our data suggest that the low levels of mutant NDRG1 is insufficient to support Schwann cells in maintaining myelin homeostasis. (C) 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license

PrP Expression, PrPSc Accumulation and Innervation of Splenic Compartments in Sheep Experimentally Infected with Scrapie

BACKGROUND: In prion disease, the peripheral expression of PrP(C) is necessary for the transfer of infectivity to the central nervous system. The spleen is involved in neuroinvasion and neural dissemination in prion diseases but the nature of this involvement is not known. The present study undertook the investigation of the spatial relationship between sites of PrP(Sc) accumulation, localisation of nerve fibres and PrP(C) expression in the tissue compartments of the spleen of scrapie-inoculated and control sheep. METHODOLOGY/PRINCIPAL FINDINGS: Laser microdissection and quantitative PCR were used to determine PrP mRNA levels and results were compared with immunohistochemical protocols to distinguish PrP(C) and PrP(Sc) in tissue compartments of the spleen. In sheep experimentally infected with scrapie, the major sites of accumulation of PrP(Sc) in the spleen, namely the lymphoid nodules and the marginal zone, expressed low levels of PrP mRNA. Double immunohistochemical labelling for PrP(Sc) and the pan-nerve fibre marker, PGP, was used to evaluate the density of innervation of splenic tissue compartments and the intimacy of association between PrP(Sc) and nerves. Some nerve fibres were observed to accompany blood vessels into the PrP(Sc)-laden germinal centres. However, the close association between nerves and PrP(Sc) was most apparent in the marginal zone. Other sites of close association were adjacent to the wall of the central artery of PALS and the outer rim of germinal centres. CONCLUSIONS/SIGNIFICANCE: The findings suggest that the degree of PrP(Sc) accumulation does not depend on the expression level of PrP(C). Though several splenic compartments may contribute to neuroinvasion, the marginal zone may play a central role in being the compartment with most apparent association between nerves and PrP(Sc)

Prion protein in myelin maintenance: What does the goat say?

publishedVersio

Prion protein in myelin maintenance: What does the goat say?

publishedVersio

Activation of innate immune genes in caprine blood leukocytes after systemic endotoxin challenge

BACKGROUND: Sepsis is a serious health problem associated with a range of infectious diseases in animals and humans. Early events of this syndrome can be mimicked by experimental administration of lipopolysaccharides (LPS). Compared with mice, small ruminants and humans are highly sensitive to LPS, making goats valuable in inflammatory models. We performed a longitudinal study in eight Norwegian dairy goats that received LPS (0.1 μg/kg, Escherichia coli O26:B6) intravenously. A control group of five goats received corresponding volumes of sterile saline. Clinical examinations were performed continuously, and blood samples were collected throughout the trial. RESULTS: Characteristic signs of acute sepsis, such as sickness behavior, fever, and leukopenia were observed within 1 h of LPS administration. A high-throughput longitudinal gene expression analysis of circulating leukocytes was performed, and genes associated with the acute phase response, type I interferon signaling, LPS cascade and apoptosis, in addition to cytokines and chemokines were targeted. Pro-inflammatory genes, such as IL1B, CCL3 and IL8, were significantly up-regulated. Interestingly, increased mRNA levels of seven interferon stimulated genes (ISGs) were observed peaking at 2 h, corroborating the increasing evidence that ISGs respond immediately to bacterial endotoxins. A slower response was manifested by four extrahepatic acute phase proteins (APP) (SAA3, HP, LF and LCN2) reaching maximum levels at 5 h. CONCLUSIONS: We report an immediate induction of ISGs in leukocytes in response to LPS supporting a link between the interferon system and defense against bacterial infections. The extrahepatic expression of APPs suggests that leukocytes contribute to synthesis of these proteins at the beginning of a systemic inflammation. Taken together, these findings provide insights into the dynamic regulation of innate immune genes, as well as raising new questions regarding the importance of ISGs and extrahepatic APPs in leukocytes after systemic endotoxin challenge. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-016-0870-x) contains supplementary material, which is available to authorized users

LPS-induced systemic inflammation reveals an immunomodulatory role for the prion protein at the blood-brain interface

Abstract Background The cellular prion protein (PrPC) is an evolutionary conserved protein abundantly expressed not only in the central nervous system but also peripherally including the immune system. A line of Norwegian dairy goats naturally devoid of PrPC (PRNP Ter/Ter) provides a novel model for studying PrPC physiology. Methods In order to explore putative roles for PrPC in acute inflammatory responses, we performed a lipopolysaccharide (LPS, Escherichia coli O26:B6) challenge of 16 goats (8 PRNP +/+ and 8 PRNP Ter/Ter) and included 10 saline-treated controls (5 of each PRNP genotype). Clinical examinations were performed continuously, and blood samples were collected throughout the trial. Genome-wide transcription profiles of the choroid plexus, which is at the blood-brain interface, and the hippocampus were analyzed by RNA sequencing, and the same tissues were histologically evaluated. Results All LPS-treated goats displayed clinical signs of sickness behavior, which were of significantly (p < 0.01) longer duration in animals without PrPC. In the choroid plexus, a substantial alteration of the transcriptome and activation of Iba1-positive cells were observed. This response included genotype-dependent differential expression of several genes associated with the immune response, such as ISG15, CXCL12, CXCL14, and acute phase proteins, among others. Activation of cytokine-responsive genes was skewed towards a more profound type I interferon response, and a less obvious type II response, in PrPC-deficient goats. The magnitude of gene expression in response to LPS was smaller in the hippocampus than in the choroid plexus. Resting state expression profiles revealed a few differences between the PRNP genotypes. Conclusions Our data suggest that PrPC acts as a modulator of certain pathways of innate immunity signaling, particularly downstream of interferons, and probably contributes to protection of vulnerable tissues against inflammatory damage