Shared and specific functions of Arfs 1–5 at the Golgi revealed by systematic knockouts

ADP-ribosylation factors (Arfs) are small GTPases regulating membrane traffic in the secretory pathway. They are closely related and appear to have overlapping functions, regulators, and effectors. The functional specificity of individual Arfs and the extent of redundancy are still largely unknown. We addressed these questions by CRISPR/Cas9-mediated genomic deletion of the human class I (Arf1/3) and class II (Arf4/5) Arfs, either individually or in combination. Most knockout cell lines were viable with slight growth defects only when lacking Arf1 or Arf4. However, Arf1+4 and Arf4+5 could not be deleted simultaneously. Class I Arfs are nonessential, and Arf4 alone is sufficient for viability. Upon Arf1 deletion, the Golgi was enlarged, and recruitment of vesicle coats decreased, confirming a major role of Arf1 in vesicle formation at the Golgi. Knockout of Arf4 caused secretion of ER-resident proteins, indicating specific defects in coatomer-dependent ER protein retrieval by KDEL receptors. The knockout cell lines will be useful tools to study other Arf-dependent processes.

Shared and specific functions of Arfs 1–5 at the Golgi revealed by systematic knockouts

The ADP-ribosylation factors (Arfs) are small GTPases regulating membrane traffic in the secretory pathway. They are closely related and appear to have overlapping functions, regulators, and effectors. The functional specificity of individual Arfs and the extent of redundancy in vivo are still largely unknown. We addressed these questions by CRISPR/Cas9-mediated genomic deletion of the human class I (Arfs 1 and 3) and class II (Arfs 4 and 5) Arfs, either individually or in combination. Cells lacking individual Arfs or certain combinations were viable with only a slight growth defect when lacking Arf1 or Arf4. However, Arf1 and 4, and Arf4 and 5 could not be deleted simultaneously. Hence, class I Arfs are not essential and Arf4 alone was found to be sufficient for cell viability. Remarkably, two single knockouts produced specific and distinct phenotypes. Upon deletion of Arf1, the Golgi complex was enlarged and recruitment of vesicle coats decreased, confirming a major role of Arf1 in coat formation at the Golgi. Cell lines deleted for Arf4 exhibited secretion of ER resident proteins, indicating a specific defect in coatomer-dependent ER protein retrieval by the KDEL receptors. The knockout cell lines will be a useful tool to study other Arf-dependent processes.

T Cell Peptides Derived from Invasive Stages of Schistosoma mansoni as Potential Schistosomiasis Vaccine

Schistosomiasis is a parasitic disease that affects 143 million people in endemic countries. This work analyzed overexpressed sequences from the cercaria phase to the early schistosomulum phase using bioinformatics tools to predict host interaction and selected proteins for predicting T cell epitopes. The final peptides were chemically synthesized, and their toxicity was evaluated in vitro. Peptides were formulated in the Adjuvant Adaptation (ADAD) vaccination system and injected into BALB/c mice that were challenged with S. mansoni cercariae to assess protection and immunogenicity. A total of 39 highly expressed S.mansoni proteins were identified as being of potential interest. Three T cell peptides predicted to bind MHC mouse and human class II were synthesized and formulated for vaccination. SmGSP and SmIKE reduced the number of eggs trapped in the liver by more than 50% in challenged BALB/c mice. The liver of mice vaccinated with either SmGSP or SmTNP had a significantly reduced affected liver surface. Transcriptome-based T cell peptides elicit partial protection and could be candidates for a multiantigen vaccine.

Analisis Dinamik Model Transmisi COVID-19 dengan Melibatkan Intervensi Karantina

This paper discusses the dynamics of COVID-19 transmission by involving quarantine interventions. The model was constructed by involving three classes of infectious causes, namely the exposed human class, asymptotically infected human class, and symptomatic infected human class. Variables were representing quarantine interventions to suppress infection growth were also considered in the model. Furthermore, model analysis is focused on the existence of equilibrium points and numerical simulations to visually showed population dynamics. The constructed model forms the SEAQIR model which has two equilibrium points, namely a disease-free equilibrium point and an endemic equilibrium point. The stability analysis showed that the disease-free equilibrium point was locally asymptotically stable at R0<1 and unstable at R0>1. Numerical simulations showed that increasing interventions in the form of quarantine could contribute to slowing the transmission of COVID-19 so that it is hoped that it can prevent outbreaks in the population.

Analisis Dinamik Model Transmisi COVID-19 dengan Melibatkan Intervensi Karantina

ABSTRAKMakalah ini membahas dinamika transmisi COVID-19 dengan melibatkan intervensi karantina. Model dikonstruksi dengan melibatkan tiga kelas penyebab infeksi, yaitu kelas manusia terpapar, kelas manusia terinfeksi tanpa gejala klinis, dan kelas manusia terinfeksi disertai gejala klinis. Variabel yang merepresentasikan intervensi karantina untuk menekan pertumbuhan infeksi juga dipertimbangkan pada model. Selanjutnya, analisis model difokuskan pada eksistensi titik kesetimbangan dan simulasi numerik untuk menunjukkan dinamika populasi secara visual. Model yang dikonstruksi membentuk model SEAQIR yang memiliki dua titik kesetimbangan, yaitu titik kesetimbangan bebas penyakit dan titik kesetimbangan endemik. Analisis kestabilan menunjukkan bahwa titik kesetimbangan bebas penyakit bersifat stabil asimtotik lokal pada saat R01 dan tidak stabil pada saat R01. Simulasi numerik menunjukkan bahwa peningkatan intervensi berupa karantina dapat berkontribusi memperlambat transmisi COVID-19 sehingga diharapkan dapat mencegah terjadinya wabah pada populasi.ABSTRACTThis paper discusses the dynamics of COVID-19 transmission by involving quarantine interventions. The model was constructed by involving three classes of infectious causes, namely the exposed human class, asymptotically infected human class, and symptomatic infected human class. Variables were representing quarantine interventions to suppress infection growth were also considered in the model. Furthermore, model analysis is focused on the existence of equilibrium points and numerical simulations to visually showed population dynamics. The constructed model forms the SEAQIR model which has two equilibrium points, namely a disease-free equilibrium point and an endemic equilibrium point. The stability analysis showed that the disease-free equilibrium point was locally asymptotically stable at R01 and unstable at R01. Numerical simulations showed that increasing interventions in the form of quarantine could contribute to slowing the transmission of COVID-19 so that it is hoped that it can prevent outbreaks in the population.

Analisis Dinamik Model Transmisi COVID-19 dengan Melibatkan Intervensi Karantina

ABSTRAKMakalah ini membahas dinamika transmisi COVID-19 dengan melibatkan intervensi karantina. Model dikonstruksi dengan melibatkan tiga kelas penyebab infeksi, yaitu kelas manusia terpapar, kelas manusia terinfeksi tanpa gejala klinis, dan kelas manusia terinfeksi disertai gejala klinis. Variabel yang merepresentasikan intervensi karantina untuk menekan pertumbuhan infeksi juga dipertimbangkan pada model. Selanjutnya, analisis model difokuskan pada eksistensi titik kesetimbangan dan simulasi numerik untuk menunjukkan dinamika populasi secara visual. Model yang dikonstruksi membentuk model SEAQIR yang memiliki dua titik kesetimbangan, yaitu titik kesetimbangan bebas penyakit dan titik kesetimbangan endemik. Analisis kestabilan menunjukkan bahwa titik kesetimbangan bebas penyakit bersifat stabil asimtotik lokal pada saat R01 dan tidak stabil pada saat R01. Simulasi numerik menunjukkan bahwa peningkatan intervensi berupa karantina dapat berkontribusi memperlambat transmisi COVID-19 sehingga diharapkan dapat mencegah terjadinya wabah pada populasi.ABSTRACTThis paper discusses the dynamics of COVID-19 transmission by involving quarantine interventions. The model was constructed by involving three classes of infectious causes, namely the exposed human class, asymptotically infected human class, and symptomatic infected human class. Variables were representing quarantine interventions to suppress infection growth were also considered in the model. Furthermore, model analysis is focused on the existence of equilibrium points and numerical simulations to visually showed population dynamics. The constructed model forms the SEAQIR model which has two equilibrium points, namely a disease-free equilibrium point and an endemic equilibrium point. The stability analysis showed that the disease-free equilibrium point was locally asymptotically stable at R01 and unstable at R01. Numerical simulations showed that increasing interventions in the form of quarantine could contribute to slowing the transmission of COVID-19 so that it is hoped that it can prevent outbreaks in the population.

PENDIDIKAN MULTIKULTURAL DAN RELEVANSINYA TERHADAP PENDIDIKAN ISLAM DI INDONESIA

Education conditions in each country is different. This could be due to differences in ethnicity, language and culture. Therefore, it is necessary education that can accept such differences through multicultural education. Multicultural education in Indonesia itself has been discourse by education experts has long since. One of those educational figures is our National Father’s Education Ki Hadjar Dewantara, who has made concepts and thoughts about multicultural education. He is an expert in the world of education and many educational concepts in Indonesia today is referring to his thoughts. The pattern of educational thought is nationalist and universal. Nationalistic, because education based on the principle of national culture, while universal is education that can be accepted and enjoyed of every human, class, race, ethnic, nation, religion and culture. So from his thoughts are focused on the teachings of character, independence, humanity and culture of the nation (multicultural).