Polymorphisms of the FCN2 Gene 3’UTR Region and Their Clinical Associations in Preterm Newborns

Ficolin-2 is regarded as an important innate immunity factor endowed with both lectin (carbohydrate recognition) qualities and ability to induce complement activation. The aim of this study was to investigate the association of the FCN2 3’-untranslated region (3’UTR) polymorphisms with ficolin-2 expression and perinatal complications in preterm neonates. The sequencing analysis allowed us to identify six 3’UTR polymorphisms with minor allele frequency (MAF) >1%: rs4521835, rs73664188, rs11103564, rs11103565, rs6537958 and rs6537959. Except for rs4521835, all adhered to Hardy-Weinberg expectations. Moreover, rs6537958 and rs6537959 were shown to be in perfect linkage disequilibrium (LD) with nine other genetic polymorphisms: rs7040372, rs7046516, rs747422, rs7847431, rs6537957, rs6537960, rs6537962, rs11462298 and rs7860507 together stretched on a distance of 1242 bp and very high LD with rs11103565. The 3’UTR region was shown to bind nuclear extract proteins. The polymorphisms at rs4521835 and rs73664188 were found to influence serum ficolin-2 concentration significantly. All polymorphisms identified create (together with exon 8 polymorphism, rs7851696) two haplotype blocks. Among 49 diplotypes (D1-D49) created from rs7851696 (G>T), rs4521835 (T>G), rs73664188 (T>C), rs11103564 (T>C), rs11103565 (G>A) and rs6537959 (T>A), twenty two occurred with frequency >1%. Two diplotypes: D13 (GTTTGT/GGTCGT) and D10 (GTTTGT/GGTCGA), were significantly more frequent among preterm neonates with early onset of infection and pneumonia, compared with newborns with no infectious complications (OR 2.69 and 2.81, respectively; both p<0.05). The minor (C) allele at rs73664188 was associated with an increased risk of very low (≤1500 g) birthweight (OR=1.95, p=0.042) but was associated with the opposite effect at rs11103564 (OR=0.11, p=0.005).

Innate immunity pathways activate cell proliferation after penetrating traumatic brain injury in adult Drosophila

We are utilizing an adult penetrating traumatic brain injury (PTBI) model in Drosophila to investigate regenerative mechanisms after damage to the central brain. We focused on cell proliferation as an early event in the regenerative process. To identify candidate pathways that may trigger cell proliferation following PTBI, we utilized RNA-Seq. We find that transcript levels for components of both Toll and Immune Deficiency (Imd) innate immunity pathways are rapidly and highly upregulated post-PTBI. We then tested mutants for the NF-κB transcription factors of the Toll and Imd pathways, Dorsal-related immunity factor (Dif) and Relish (Rel) respectively. We find that loss of either or both Dif and Rel results in loss of cell proliferation after injury. We then tested canonical downstream targets of Drosophila innate immune signaling, the antimicrobial peptides (AMPs), and find that they are not required for cell proliferation following PTBI. This suggests that there are alternative targets of Toll and Imd signaling that trigger cell division after injury. Furthermore, we find that while AMP levels are substantially elevated after PTBI, their levels revert to near baseline within 24 hours. Finally, we identify tissue-specific requirements for Dif and Rel. Taken together, these results indicate that the innate immunity pathways play an integral role in the regenerative response. Innate immunity previously has been implicated as both a potentiator and an inhibitor of regeneration. Our work suggests that modulation of innate immunity may be essential to prevent adverse outcomes. Thus, this work is likely to inform future experiments to dissect regenerative mechanisms in higher organisms.

COVID-19 Pandemic: Age and Temperature Related Effects

Background: Coronavirus belongs to the phylum- incertae sedis, order- nidovirales, family- coronaviridae, and the subfamily-orthocononaviridae. Coronaviruses spring up from the family of viruses that can cause malady such as the common cold, fever, shortness of breath, aches, chills, loss of smell, etc. Objective: As we all know coronavirus has affected the whole world and many of the affected patients has led to death. As the prevalence of this disease has raised, many myths has also originated like the effect of temperature on the virus; is this virus surely killed by effect of temperature? Is the effect of this virus is more on the old age patients? In the presented compilation, we have tried to exposé the actual reality behind these all myths and also tried to find the morphologic difference of coronavirus from the other viruses. Methods: The recent updates on this virus have been obtained from search engines like Pub med and Google scholar, by using COVID-19, coronavirus, Pandemic corona keywords. Results: After a huge search on the temperature effect on this disease; it was evident that there is no effect of temperature on the coronavirus. Due to the immunity factor, it showed its worst effect on old age people in many countries. Conclusion: The structure, symptoms and incubation period of coronavirus have been given in this review article. We have summarized how the coronavirus is different from others and the effects of temperature and old age have been also discussed.

Cation channel conductance and pH gating of the innate immunity factor APOL1 are governed by pore-lining residues within the C-terminal domain

The human innate immunity factor apolipoprotein L-I (APOL1) protects against infection by several protozoan parasites, including Trypanosoma brucei brucei. Endocytosis and acidification of high-density lipoprotein–associated APOL1 in trypanosome endosomes leads to eventual lysis of the parasite due to increased plasma membrane cation permeability, followed by colloid-osmotic swelling. It was previously shown that recombinant APOL1 inserts into planar lipid bilayers at acidic pH to form pH-gated nonselective cation channels that are opened upon pH neutralization. This corresponds to the pH changes encountered during endocytic recycling, suggesting APOL1 forms a cytotoxic cation channel in the parasite plasma membrane. Currently, the mechanism and domains required for channel formation have yet to be elucidated, although a predicted helix-loop-helix (H-L-H) was suggested to form pores by virtue of its similarity to bacterial pore-forming colicins. Here, we compare recombinant human and baboon APOL1 orthologs, along with interspecies chimeras and individual amino acid substitutions, to identify regions required for channel formation and pH gating in planar lipid bilayers. We found that whereas neutralization of glutamates within the H-L-H may be important for pH-dependent channel formation, there was no evidence of H-L-H involvement in either pH gating or ion selectivity. In contrast, we found two residues in the C-terminal domain, tyrosine 351 and glutamate 355, that influence pH gating properties, as well as a single residue, aspartate 348, that determines both cation selectivity and pH gating. These data point to the predicted transmembrane region closest to the APOL1 C terminus as the pore-lining segment of this novel channel-forming protein.

AL-‘ULAMĀ’ WARATHAT AL-ANBIYĀ’: Modernity and Nurture of Authority in Aceh Society

<p><span lang="IN">This paper aims to analyze the immunity factor of Acehnese loyalty to the <em>ulama</em>. Generally, if the <em>ulama</em> fail to respond to problems that arise in modernity, they are abandoned by society. Modernization is taking place very quickly in Aceh. In Aceh, even though the <em>ulama</em> were unable to respond to modernity, they were never abandoned by the community. The type of modernization that is the focus of the author's observation is development, politics, and economics which includes banking and trade. Using a qualitative approach, this study finds, that is in Aceh, precisely because the <em>ulama</em> do not respond to modernity, the immunity of loyalty to the <em>ulama</em> can continue. In Aceh, secular-minded society, they give authority to experts in their respective fields. Because the <em>ulama</em> are treated as religious experts, then when they do not respond to other fields such as development, politics, economics and other fields, they become respected. Although only given space in the field of religion, the position of the <em>ulama</em> remains very important in Aceh because religion is a very important part of the life of the Acehnese people</span></p>

OSTEORADIONEKROSIS PASCA EKSTRAKSI GIGI PASIEN DENGAN RIWAYAT KANKER NASOFARING

Background: Osteoradionecrosis (ORN) post dental extraction is post dentalextraction complication with post radiation cancer theraphy. Objective : to present rare case, ORN post dental extraction with post radiation Ca nasopharing therapy 3 years ago.Case Management: A 54 years old patient reported to the dental out-patient department with a chief complaint of pus discharge from right buccal since post dental extraction 6 months ago. He gave a history of a nasopharing Carcinoma with histopatology as squamous cell carcinoms 3 years ago and radio therapy but no surgery. Intraoral examination, exposed necrotic bone found from right lower retromolar area 46 with pus discharge. Radiographic view was likely squester. Local surgical debridement and the sequestrectomy was undertaken with general anaesthesia. Antibiotic injection treatment was ceftriaxon 2x 1gram, infus metronidazol 3x500 mg and ketorolac 3x1 ampul, the patient was treated for 3 days and educated to maintain his oral hygiene with povidone iodine gargle.Discussion: Osteoradionecrosis (ORN) is late effect of radiation therapy thatresults in irreversible tissue death, which is clinically observed as bony exposure for more than 3 months duration. The mandible is affected more often than the maxilla or any other bones of head and neck region. The incidence of ORN in the mandible is reported to be between 2% and 22% and most often affects the body of the mandible. Ideal time is one year minimal post radiotherapy to get maximal vascularization for optimal healing. But immunity factor and radiation doses can trigger emergense ORN.Conclusion: Need time consideration, clinic analysis and pathologys before doing dental extraction for post radiotherapy cancer cases to prevent ORN.

Analysis of Vibrio cholerae genomes using a novel bioinformatic tool identifies new, active Type VI Secretion System gene clusters

BackgroundLike many bacteria, Vibrio cholerae, which causes fatal cholera, deploys a harpoon-like Type VI Secretion System (T6SS) to compete against other microbes in environmental and host settings. The T6SS punctures adjacent cells and delivers toxic effector proteins that are harmless to bacteria carrying cognate immunity factors. Only four effector/immunity pairs encoded on one large and three auxiliary gene clusters have been characterized from largely clonal, patient-derived strains of V. cholerae.ResultsWe sequenced two dozen V. cholerae strain genomes from diverse sources and developed a novel and adaptable bioinformatic tool based on Hidden Markov Models. We identified two new T6SS auxiliary gene clusters; one, Aux 5, is described here. Four Aux 5 loci are present in the host strain, each with an atypical effector/immunity gene organization. Structural prediction of the putative effector indicated it is a lipase, which we name TleV1 (Type VI lipase effector Vibrio, TleV1). Ectopic TleV1 expression induced toxicity in E. coli, which was rescued by co-expression of the TleV1 immunity factor. A clinical V. cholerae reference strain expressing the Aux 5 cluster used TleV1 to lyse its parental strain upon contact via its T6SS but was unable to kill parental cells expressing TleV1’s immunity factor.ConclusionWe developed a novel bioinformatic method and identified new T6SS gene clusters in V. cholerae. We also showed the TleV1 toxin is delivered in a T6SS-manner by V. cholerae and can lyse other bacterial cells. Our web-based tool may be modified to identify additional novel T6SS genomic loci in diverse bacterial species.

Mammalian STT3A/B oligosaccharyltransferases segregate N-glycosylation at the translocon from lipid-linked oligosaccharide hydrolysis

Oligosaccharyltransferases (OSTs) N-glycosylate proteins by transferring oligosaccharides from lipid-linked oligosaccharides (LLOs) to asparaginyl residues of Asn-Xaa-Ser/Thr acceptor sequons. Mammals have OST isoforms with STT3A or STT3B catalytic subunits for cotranslational or posttranslational N-glycosylation, respectively. OSTs also hydrolyze LLOs, forming free oligosaccharides (fOSs). It has been unclear whether hydrolysis is due to one or both OSTs, segregated from N-glycosylation, and/or regulated. Transfer and hydrolysis were assayed in permeabilized HEK293 kidney and Huh7.5.1 liver cells lacking STT3A or STT3B. Transfer by both STT3A-OST and STT3B-OST with synthetic acceptors was robust. LLO hydrolysis by STT3B-OST was readily detected and surprisingly modulated: Without acceptors, STT3B-OST hydrolyzed Glc3Man9GlcNAc2-LLO but not Man9GlcNAc2-LLO, yet it hydrolyzed both LLOs with acceptors present. In contrast, LLO hydrolysis by STT3A-OST was negligible. STT3A-OST however may be regulatory, because it suppressed STT3B-OST–dependent fOSs. TREX1, a negative innate immunity factor that diminishes immunogenic fOSs derived from LLOs, acted through STT3B-OST as well. In summary, only STT3B-OST hydrolyzes LLOs, depending upon LLO quality and acceptor site occupancy. TREX1 and STT3A suppress STT3B-OST–dependent fOSs. Without strict kinetic limitations during posttranslational N-glycosylation, STT3B-OST can thus moonlight for LLO hydrolysis. In contrast, the STT3A-OST/translocon complex preserves LLOs for temporally fastidious cotranslational N-glycosylation.

Crystal structure of the mouse innate immunity factor bacterial permeability-increasing family member A1

Bacterial permeability-increasing family member A1 (BPIFA1) is an innate immunity factor and one of the most abundantly secreted proteins in the upper airways. BPIFA1 is multifunctional, with antimicrobial, surfactant and lipopolysaccharide-binding activities, as well as established roles in lung hydration. Here, the 2.5 Å resolution crystal structure of BPIFA1 from Mus musculus (mBPIFA1) is presented and compared with those of human BPIFA1 (hBPIFA1) and structural homologs. Structural distinctions between mBPIFA1 and hBPIFA1 suggest potential differences in biological function, including the regulation of a key pulmonary ion channel.