Interactive Regulation of Hormone and Resistance Gene in Proline Metabolism Is Involved in Effector-Triggered Immunity or Disease Susceptibility in the Xanthomonas campestris pv. campestris–Brassica napus Pathosystem

To characterize cultivar variations in hormonal regulation of the transition between pattern-triggered immunity (PTI) and effector-triggered immunity or susceptibility (ETI or ETS), the responses of resistance (R-) genes, hydrogen peroxide, and proline metabolism in two Brassica napus cultivars to contrasting disease susceptibility (resistant cv. Capitol vs. susceptible cv. Mosa) were interpreted as being linked to those of endogenous hormonal levels and signaling genes based on a time course of disease symptom development. Disease symptoms caused by the Xanthomonas campestris pv. campestris (Xcc) infections were much more developed in cv. Mosa than in cv. Capitol, as shown by an earlier appearance (at 3 days postinoculation [3 DPI]) and larger V-shaped necrosis lesions (at 9–15 DPI) in cv. Mosa. The cultivar variations in the R-genes, hormone status, and proline metabolism were found in two different phases (early [0–3 DPI] and later [9–15 DPI]). In the early phase, Xcc significantly upregulated PTI-related cytoplasmic kinase (Botrytis-induced kinase-1 [BIK1]) expression (+6.3-fold) with salicylic acid (SA) accumulation in cv. Capitol, while relatively less (+2.6-fold) with highly increased jasmonic acid (JA) level in cv. Mosa. The Xcc-responsive proline accumulation in both cultivars was similar to upregulated expression of proline synthesis-related genes (P5CS2 and P5CR). During the later phase in cv. Capitol, Xcc-responsive upregulation of ZAR1 (a coiled-coil-nucleotide binding site-leucine-rich repeat [CC-NB-LRR-type R-gene]) was concomitant with a gradual increase in JA levels without additional proline accumulation. However, in cv. Mosa, upregulation of TAO1 (a toll/interleukin-1 receptor-nucleotide binding site-leucine-rich repeat [TIR-NB-LRR-type R-gene]) was consistent with an increase in SA and abscisic acid (ABA) levels and resulted in an antagonistic depression of JA, which led to a proline accumulation. These results indicate that Xcc-induced BIK1- and ZAR1-mediated JA signaling interactions provide resistance and confirm ETI, whereas BIK1- and TAO1-enhanced SA- and/or ABA-mediated proline accumulation is associated with disease susceptibility (ETS).

Splicing QTL analysis focusing on coding sequences reveals pathogenicity of disease susceptibility loci.

Splicing QTL (sQTL) are one of the major causal mechanisms in GWAS loci, but their role in disease pathogenesis is poorly understood. One reason is the huge complexity of alternative splicing events producing many unknown isoforms. Here, we proposed two novel approaches, namely integration and selection, for this complexity by focusing on protein-structure of isoforms. First, we integrated isoforms with the same coding sequence (CDS) and identified 369-601 integrated-isoform ratio QTLs (i2-rQTLs), which altered protein-structure, in six immune subsets. Second, we selected CDS incomplete isoforms annotated in GENCODE and identified 175-337 isoform-ratio QTL (i-rQTL). By comprehensive long-read capture RNA-seq among these incomplete isoforms, we revealed 29 full-length isoforms with novel CDSs associated with GWAS traits. Furthermore, we have shown that disease-causal sQTL genes can be identified by evaluating their trans-eQTL effects. Our approaches highlight the understudied role of protein-altering sQTLs and are broadly applicable to other tissues and diseases.

HUBUNGAN ANTARA PEMBERIAN MP ASI DI BAWAH USIA 6 BULAN DENGAN KERENTANAN PENYAKIT DI DESA PAYUNG AGUNG KECAMATAN PANUMBANGAN KABUPATEN CIAMIS

MP-ASI (Makanan Pendamping-Air Susu Ibu) adalah makanan atau minuman selain ASI yang mengandung nutrisi yang diberikan kepada bayi setelah bayi siap atau berusia 6 bulan. Makanan pendamping ASI merupakan makanan tambahan bagi bayi.Makanan ini harus menjadi pelengkap dan dapat memenuhi kebutuhan bayi. Jadi selain makanan pendamping ASI, ASI harus tetap diberikan kepada bayi paling tidak sampai usia 24 bulan. Hasil Survei Demografi dan Kesehatan Indonesia (SDKI) tahun 2013 diketahui bahwa pemberian ASI Ekslusif hanya meningkat sekitar 10% dalam periode 2007-2013. Pada SDKI tahun 2007 angka pemberian ASI Ekslusif itu hanya sekitar 32%, dan di SDKI tahun 2013 meningkat menjadi 42%, meskipun ada peningkatan hal ini masih jauh dari angka sempurna. Keberhasilan ASI Ekslusif di Jawa Barat tercapai 42% dari target 80%. Tujuan penelitian ini adalah untuk mengetahui hubungan antara pemberian MP ASI kurang dari 6 bulan dengan kerentanan penyakit di Desa Payung Agung Kecamatan Panumbangan Kabupaten Ciamis tahun 2014. Jenis penelitian yaitu menggunakan survey analitik dengan pendekatan case control (retrospective). Populasi pada penelitian ini adalah seluruh ibu yang memiliki balita di Desa Payung Agung Kecamatan Panumbangan Kabupaten Ciamis periode Februari Mei 2014 sebanyak 357 orang. Teknik pengambilan sampel pada penelitian ini adalah Proporsional Random Sampling sebanyak 78 orang. Hasil penelitian diketahui pemberian MP ASI adalah kategori memberikan MP ASI dibawah usia 6 bulan sebanyak 55 orang (10,5%), kerentanan penyakit adalah kategori mengalami sebanyak 58 orang (74,4%) dan terdapat hubungan antara pemberian MP ASI dibawah usia 6 bulan dengan kerentanan penyakit di Desa Payung Agung Kecamatan Panumbangan Kabupaten Ciamis 2014 ditunjukan dengan nilai p value 0,000 < α (0,05). Kesimpulan penelitian ini adalah sebagian besar memberikan MP ASI dibawah usia 6 bulan, sebagian besar mengalami kerentan penyakit dan terdapat hubungan antara pemberian MP ASI dibawah usia 6 bulan dengan kerentanan penyakit di Desa Payung Agung Kecamatan Panumbangan Kabupaten Ciamis 2014.MP-ASI (Companion Food-Breast Milk) is food or drink other than ASI that contains nutrients given to the baby after the baby is ready or 6 months old. Breast milk companion food is a supplement for babies. This food should be complementary and can meet the needs of the baby. So in addition to breast milk supplements, breast milk should still be given to babies at least until the age of 24 months. The results of the Indonesian Demographic and Health Survey (SDKI) in 2013 found that Exclusive Breastfeeding increased only about 10% in the period 2007-2013. In SDKI in 2007 the number of exclusive breastfeeding was only about 32%, and in SDKI in 2013 increased to 42%, although there is an increase this is still far from the perfect figure. The success of Exclusive Breastfeeding in West Java reached 42% of the target of 80%. The purpose of this study is to find out the relationship between the provision of MP ASI less than 6 months with the susceptibility to disease in Payung Agung Village, Panumbangan District, Ciamis Regency in 2014. This type of research is to use analytical surveys with case control (retrospective) approach. The population in this study is all mothers who have a toddler in Payung Agung Village, Panumbangan District, Ciamis Regency in the period of February May 2014 as many as 357 people. The sampling technique in this study is Proportional Random Sampling of 78 people. The results of the study are known that the provision of ASI MPs is a category of giving ASI MPs under the age of 6 months as many as 55 people (10.5%), the susceptibility of the disease is the category of experiencing as many as 58 people (74.4%) and there is a relationship between the provision of with disease susceptibility in Payung Agung Village, Panumbangan Subdistrict, Ciamis Regency 2014 is shown with a p value of 0,000 < α (0.05). The conclusion of this study is that most of them give ASI MPs under the age of 6 months, most of them have a susceptibility to disease and there is a relationship between giving ASI MPs under the age of 6 months with susceptibility to disease in Payung Agung Village, Panumbangan District, Ciamis Regency 2014.

Role of Interferon-Gamma +874 A/T Single-Nucleotide Polymorphism and Tuberculosis Susceptibility of Pediatric Population in North Sumatera, Indonesia

BACKGROUND: Tuberculosis (TB) remains to be a leading cause of morbidity and mortality worldwide. The immune defense against Mycobacterium tuberculosis (M. tuberculosis) is complicated. Interferon gamma (IFN-g) is the main cytokine involved in the immune response of TB. To date, the role of +874 A/T single nucleotide polymorphism (SNP) and TB disease susceptibility continue to be controversial. OBJECTIVES: The aim of this study was to investigate the role of +874 A/T SNP and TB disease susceptibility of pediatric population in North Sumatera, Indonesia METHODS: A case control study was conducted in Medan and Batubara, North Sumatera, Indonesia from January to December 2016. A total of 51 children with TB and 51 healthy controls were enrolled in this study. Subjects were 2 months to 14 years old age children diagnosed with TB and written informed consent from the parents or the caregivers to participate. Subjects were withdrawn from the study when immunodeficiency condition was found or suffered from other infection disease. DNA samples were obtained from all of the subjects. +874 A/T SNP was identified by performing the amplification refractory mutational system - polymerase chain reaction (ARMS-PCR) method. IFN-g levels were measured by using human enzyme-linked immunosorbent assay/ELISA. Data analysis was performed using chi square and Mann Whitney test. p value <0.05 was considered significant. RESULTS: The result of this study reveals the presence of AA, AT and TT genotype in TB patients were 31 (60.8%), 20 (39.2%) and 0 (0%); respectively (p=0.023). Significant decreased production of IFN-g levels (p=0.042) were found in TB patients 9.41 (1.10 – 28.06) pg/ml. CONCLUSION: Our study demonstrated significant evidence of the role of +874 A/T SNP and TB disease susceptibility of pediatric population in North Sumatera, Indonesia predominantly AA genotype. Significant decreased production of IFN-g reported among pediatric TB.

RNA binding protein DDX5 directs tuft cell specification and function to regulate microbial repertoire and disease susceptibility in the intestine

ObjectiveTuft cells residing in the intestinal epithelium have diverse functions. In the small intestine, they provide protection against inflammation, combat against helminth and protist infections, and serve as entry portals for enteroviruses. In the colon, they had been implicated in tumourigenesis. Commitment of intestinal progenitor cells to the tuft cell lineage requires Rho GTPase Cell Division Cycle 42 (CDC42), a Rho GTPase that acts downstream of the epidermal growth factor receptor and wingless-related integration site signalling cascades, and the master transcription factor POU class 2 homeobox 3 (POU2F3). This study investigates how this pathway is regulated by the DEAD box containing RNA binding protein DDX5 in vivo.DesignWe assessed the role of DDX5 in tuft cell specification and function in control and epithelial cell-specific Ddx5 knockout mice (DDX5ΔIEC) using transcriptomic approaches.ResultsDDX5ΔIEC mice harboured a loss of intestinal tuft cell populations, modified microbial repertoire, and altered susceptibilities to ileal inflammation and colonic tumourigenesis. Mechanistically, DDX5 promotes CDC42 protein synthesis through a post-transcriptional mechanism to license tuft cell specification. Importantly, the DDX5-CDC42 axis is parallel but distinct from the known interleukin-13 circuit implicated in tuft cell hyperplasia, and both pathways augment Pou2f3 expression in secretory lineage progenitors. In mature tuft cells, DDX5 not only promotes integrin signalling and microbial responses, it also represses gene programmes involved in membrane transport and lipid metabolism.ConclusionRNA binding protein DDX5 directs tuft cell specification and function to regulate microbial repertoire and disease susceptibility in the intestine.

Genetic Variants of the NF-κB Pathway: Unraveling the Genetic Architecture of Psoriatic Disease

Psoriasis is a multifactorial genetic disease for which the genetic factors explain about 70% of disease susceptibility. Up to 30–40% of psoriasis patients develop psoriatic arthritis (PsA). However, PsA can be considered as a “disease within a disease”, since in most cases psoriasis is already present when joint complaints begin. This has made studies that attempt to unravel the genetic basis for both components of psoriatic disease enormously difficult. Psoriatic disease is also accompanied by a high burden of comorbid conditions, mainly of the cardiometabolic type. It is currently unclear whether these comorbidities and psoriatic disease have a shared genetic basis or not. The nuclear factor of kappa light chain enhancer of activated B cells (NF-κB) is a transcription factor that regulates a plethora of genes in response to infection, inflammation, and a wide variety of stimuli on several cell types. This mini-review is focused on recent findings that highlight the importance of this pathway both in the susceptibility and in the determinism of some features of psoriatic disease. We also briefly review the importance of genetic variants of this pathway as biomarkers of pharmacological response. All the above may help to better understand the etiopathogenesis of this complex entity.