Nlrp6 promotes recovery after peripheral nerve injury independently of inflammasomes

Background: NOD-like receptors (Nlrs) are key regulators of immune responses during infection and autoimmunity. A subset of Nlrs assembles inflammasomes, molecular platforms that are activated in response to endogenous danger and microbial ligands and that control release of interleukin (IL)-1 beta and IL-18. However, their role in response to injury in the nervous system is less understood. Methods: In this study, we investigated the expression profile of major inflammasome components in the peripheral nervous system (PNS) and explored the physiological role of different Nlrs upon acute nerve injury in mice. Results: While in basal conditions, predominantly members of NOD-like receptor B (Nlrb) subfamily (NLR family, apoptosis inhibitory proteins (NAIPs)) and Nlrc subfamily (ICE-protease activating factor (IPAF)/NOD) are detected in the sciatic nerve, injury causes a shift towards expression of the Nlrp family. Sterile nerve injury also leads to an increase in expression of the Nlrb subfamily, while bacteria trigger expression of the Nlrc subfamily. Interestingly, loss of Nlrp6 led to strongly impaired nerve function upon nerve crush. Loss of the inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC) and effector caspase-1 and caspase-11 did not affect sciatic nerve function, suggesting that Nlrp6 contributed to recovery after peripheral nerve injury independently of inflammasomes. In line with this, we did not detect release of mature IL-1 beta upon acute nerve injury despite potent induction of pro-IL-1 beta and inflammasome components Nlrp3 and Nlrp1. However, Nlrp6 deficiency was associated with increased pro-inflammatory extracellular regulated MAP kinase (ERK) signaling, suggesting that hyperinflammation in the absence of Nlrp6 exacerbated peripheral nerve injury. Conclusions: Together, our observations suggest that Nlrp6 contributes to recovery from peripheral nerve injury by dampening inflammatory responses independently of IL-1 beta and inflammasomes

La hermenéutica según Hans-Georg Gadamer y su aporte a la educación / Hermeneutics as Hans-Georg Gadamer and his contribution to education

En este artículo se resume la historia intelectual de la corriente filosófica de la hermenéutica, como fue concebido por el filósofo Hans-Georg Gadamer en su estudio Verdad y Método. Aclara algunos conceptos claves de la filosofía hermenéutica de Gadamer, enfoca la articulación del conocimiento humano que se apoya en la teoría aristotélica del conocimiento, para cuestionar la influyente obra de síntesis del conocimiento de Immanuel Kant. Desde la articulación de conocimientos de Gadamer se ofrecen algunas sugerencias para la concepción y para la práctica de la educación.In this article the intellectual history of philosophical hermeneutics is summarized, as conceived by the philosopher Hans-Georg Gadamer in his study Truth and Method. Clarifies some key concepts of the hermeneutic philosophy of Gadamer, focus articulation of human knowledge that is based on the aristotelian theory of knowledge, to question the influential work of synthesis of knowledge of Immanuel Kant. Since the articulation of knowledge of Gadamer some suggestions for the design and practice of education offere

Strategi Pengelolaan Terpadu Fasilitas Pejalan Kaki

Ketiadaan dan/atau buruknya kualitas layanan fasilitas pejalan kaki tidak saja berdampak pada gangguan kelancaran aktivitas pejalan kaki tetapi juga dapat memicu terjadinya kecelakaan lalu lintas. Di lokasi studi sesungguhnya sudah terdapat sejumlah fasilitas yaitu trotoar, zebra cross, Zona Selamat Sekolah (ZoSS), halte dan jembatan penyeberangan; namun hasil observasi menunjukkan bahwa selain terjadi kemacetan akibat pola parkir kendaraan dan penyeberangan pejalan kaki yang tidak teratur, juga terindikasi adanya risiko kecelakaan akibat perilaku speeding pengendara sepeda motor. Studi ini tidak saja bertujuan untuk mengidentifikasi aspek ketersediaan (jumlah), dimensi dan tata letak, namun juga kebutuhan pengembangannya secara berkelanjutan. Penilaian kinerja dilakukan berdasarkan pertimbangan akan aspek ketersediaan dan aspek fungsionalnya yaitu dengan membandingkannya terhadap kriteria penyediaan maupun kriteria desain tiap fasilitas dimaksud. Hasil penelitian menunjukkan bahwa diperlukan tidak saja perbaikan fisik dan tambahan fasilitas namun juga dimensi dan tata letaknya

Non-classical ProIL-1beta activation during mammary gland infection is pathogen-dependent but caspase-1 independent

Infection of the mammary gland with live bacteria elicits a pathogen-specific host inflammatory response. To study these host-pathogen interactions wild type mice, NF-kappaB reporter mice as well as caspase-1 and IL-1beta knockout mice were intramammarily challenged with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The murine mastitis model allowed to compare the kinetics of the induced cytokine protein profiles and their underlying pathways. In vivo and ex vivo imaging showed that E. coli rapidly induced NF-kappaB inflammatory signaling concomitant with high mammary levels of TNF-alpha, IL-1 alpha and MCP-1 as determined by multiplex analysis. In contrast, an equal number of S. aureus bacteria induced a low NF-kappaB activity concomitant with high mammary levels of the classical IL-1beta fragment. These quantitative and qualitative differences in local inflammatory mediators resulted in an earlier neutrophil influx and in a more extensive alveolar damage post-infection with E. coli compared to S. aureus. Western blot analysis revealed that the inactive proIL-1beta precursor was processed into pathogen-specific IL-1beta fragmentation patterns as confirmed with IL-1beta knockout animals. Additionally, caspase-1 knockout animals allowed to investigate whether IL-1beta maturation depended on the conventional inflammasome pathway. The lack of caspase-1 did not prevent extensive proIL-1beta fragmentation by either of S. aureus or E. coli. These non-classical IL-1beta patterns were likely caused by different proteases and suggest a sentinel function of IL-1beta during mammary gland infection. Thus, a key signaling nodule can be defined in the differential host innate immune defense upon E. coli versus S. aureus mammary gland infection, which is independent of caspase-1

PRAGMATIC ALTERNATIVE CONSTRUCTION (FRONTING, LEFT DISLOCATION, AND TOPICALIZATION) IN LAMALERA DIALECT

Abstract Left dislocation construction, fronting construction and topicalization construction are universal linguistic alternations. Nevertheless these three constructions have characteristics that are very different from one language to another. This distinction depends on the language system of every language. This research data is obtained from the result of conversation between speakers of Lamaholot dialect of Lamalera. The result of data analysis proves that LDLL has three alternative constructions. The use of real language in everyday communication, this alternative construction ear has a gradative usage frequency. Left dislocation construction has the lowest usage frequency while the construction of precision and topicalization construction is significant. However, the construction of forging and parsing differed from one to another. Left dislocation construction is the advancement of peripheral arguments while topicalization construction is the construction of core argument prediction. The construction of topicalization is a passive-like construction (derivative construction). Keywords: Left dislocation construction, fronting construction and topicalization constructio

Caspase-1 engagement and TLR-induced c-FLIP expression suppress ASC/caspase-8-dependent apoptosis by inflammasome sensors NLRP1b and NLRC4

The caspase activation and recruitment domain (CARD)-based inflammasome sensors NLRP1b and NLRC4 induce caspase-1-dependent pyroptosis independent of the inflammasome adaptor ASC. Here, we show that NLRP1b and NLRC4 trigger caspase-8-mediated apoptosis as an alternative cell death program in caspase-1(-/-) macrophages and intestinal epithelial organoids (IECs). The caspase-8 adaptor FADD was recruited to ASC specks, which served as cytosolic platforms for caspase-8 activation and NLRP1b/NLRC4-induced apoptosis. We further found that caspase-1 protease activity dominated over scaffolding functions in suppressing caspase-8 activation and induction of apoptosis of macrophages and IECs. Moreover, TLR-induced c-FLIP expression inhibited caspase-8-mediated apoptosis downstream of ASC speck assembly, but did not affect pyroptosis induction by NLRP1b and NLRC4. Moreover, unlike during pyroptosis, NLRP1b- and NLRC4-elicited apoptosis retained alarmins and the inflammasome-matured cytokines interleukin 1 beta (IL-1 beta) and IL-18 intracellularly. This work identifies critical mechanisms regulating apoptosis induction by the inflammasome sensors NLRP1b and NLRC4 and suggests converting pyroptosis into apoptosis as a paradigm for suppressing inflammation

ANALISIS PRODUKTIVITAS PEKERJA PADA PROYEK PEMBANGUNAN GEDUNG DPRD KOTA SAMARINDA KALIMANTAN TIMUR

Produktivitas merupakan faktor mendasar yang mempengaruhi performasi kemampuan bersaing dalam industri kontruksi. Produktivitastenagakerjaakansangatberpengaruhjugaterhadapbesarnyakeuntunganataukerugiansuatupr oyek.Dalam mengukur tingkat produktivitas tenaga kerja ada berbagai macam cara, salah satunya dengan meneliti besarnya tingkat LUR ( Labour Utilitation Rate ) masing-masing pekerja, yaitu meneliti sampai seberapa besar tingkat efektivitas para pekerja dala bekerja. Penelitian ini dilakukan menggunakan metode uji validitas, uji realibilitas, uji normalitas, uji regresi dan uji hipotesis.Dimana data diperoleh dengan mengumpulkan data primer dan data sekunder, yang kemudian dianalisis menggunakan metode statistika parametris dengan bantuan program SPSS. Berdasarkan hasil penelitian yang dilakukan, Analisis Produktivitas Pekerja Pada Proyek Gedung Kantor DPRD kotasamarinda Kalimantan timurmasihbanyakkendala yang mempengaruhi produktivitas pekerja pada proyek tersebu

Ri'e Hikun Liman Wanan Communication Media with Rera Wulan Tana Ekan

The traditional people's belief in God as the Supreme Cause of the universe can be expressed in various ways. The methods used are the inner representation of traditional society of the existence of a God who created the heavens and the earth. The Lamaholot people refer to God as Rera Wulan Tana Ekan 'Creator of Heaven and Earth' in a cultural perspective. Rera Wulan Tana Ekan in the perspective of Lamaholot culture is the Highest Being who is believed to have perfect abilities such as creating, maintaining, maintaining, even destroying. These particularities of Rera Wulan Tana Ekan are the basis for the importance of intense communication between humans and Rera Wulan Tana Ekan God’. Ri'e Hikun Liman Wanan ‘right hand corner of the house’ is a medium of human communication with Rera Wulan Tana Ekan ‘God’