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One of the most farmed fishes is the African catfish, Clarias gariepinus . Its production has increased by 20% annually on average during the last 20 years, but the occurrence of fish diseases, especially bacterial such as Aeromonas hydrophila infections, is hindering its activities. Also, the incorporation of plant-derived substances in aquafeeds is limited since they frequently contain different antinutritional factors, like nonstarch polysaccharides (NSPs). However, supplementing fish diets with β -mannanase could increase growth, antioxidants, and immunity. Despite the advantage of β -mannanase, its effects on growth, digestive enzymes, antioxidants, and immunity in African catfish need to be elucidated. This study examined the effects of dietary β-mannanase on the growth performance, liver enzymes, antioxidant profiles, immunity, and protection of African catfish, C. gariepinus , against A. hydrophila infection. Five isonitrogenous diets were prepared to have 400 g/kg crude protein and supplemented with β -mannanase at 0, 1500, 3000, 4500, or 6000 thermostable endo, 1,4- β -mannanase units (TMUs)/kg diet and fed to 300 juveniles of the African catfish, C. gariepinus (mean weight 12.1 ± 0.1 g) for 12 weeks. Then, 10 fish from each tank received an intraperitoneal injection of 0.1 mL of A. hydrophila (5.0 × 10 5  CFU/mL) and observed for 14 days. Results showed dietary β -mannanase levels considerably improved growth performance but did not affect fish survival. Also, amylase, protease, and lipase levels were significantly promoted in the fish fed with β -mannanase-fortified diets than the control group ( p   < 0.05). Enhanced gut villi and intestinal absorption areas, haematlogical profiles, and liver enzymes but reduced gut viscosity were observed in fish-fed β -mannanase-fortified diets ( p   < 0.05). In a dose-dependent order, including β -mannanase in the meals of African catfish raised the levels of glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione-S-transferase (GST), and glutamate cysteine ligase (GCL) activities and decreased the malondialdehyde (MDA) values in African catfish ( p   < 0.05). Also, fish immunity was greatly ( p   < 0.05) enhanced due to supplementation of the diet with β -mannanase. In addition, fish-fed diets comprising 6000 TMU β -mannanase/kg diet showed the lowest rates of fish mortality (7.5%) ( p   < 0.05). Therefore, feeding African catfish, Clarias gariepinus , β -mannanase enhanced growth performance, increased activity of digestive enzymes, gut morphology, enhanced generation of short-chain fatty acids, digesta potential of hydrogen (pH), and improved antioxidant profiles and immunity at the optimum dose of 5800 TMU/kg diet. Additionally, β -mannanase protected African catfish against A. hydrophila infection., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Ibrahim Adeshina et al.)

The effects of dietary Lagnaria breviflora leaves extract (LBLE) on the growth performance, feed utilisation and haematological parameters of juveniles African catfish, Clarias gariepinus (mean = 8.45 ± 0.6 g) raised in a flow water (mean temperature 26.7°C, mean pH 7.52, mean dissolved oxygen 6.05 mg/L) were assessed in this study. Diets (400 g/kg crude protein; 4631.5 kcal/kg gross energy) supplemented with LBLE at levels of 0 (control), 0.5, 1.0, 1.5 or 2.0 g/kg diet were served to fish in triplicates (each replicate has 20 fish) until they appeared satiated for 12 weeks. Then, they were challenged with Aeromonas hydrophila infection for further 2 weeks. Fish served dietary LBLE had considerable higher weight gain (64.76 g) and specific growth rate (765.5% g/day) than the fish group fed with the control diet with a reduced feed conversion ratio (1.45) (p < 0.05). Compared to fish fed with the control diet, the villi height (146.30 µm) and width (284.35 µm) of the intestines increased greatly in a dose (LBLE in diets) dependent order. Similarly, dietary LBLE increased (p < 0.05) the packed cell volume (46.11%) and haemoglobin (17.03 g/dL), whereas 1.5 g of LBLE increased the counts of white blood cells. Glutathione S-transferase (769.43 U/mg protein), glutathione peroxidase (84.14 U/mg protein) and superoxide dismutase (433.15 U/mg protein) activities were significantly higher (p < 0.05) in fish fed with diets supplemented with LBLE compared to the control one. Additionally, dietary LBLE increased phagocytic and lysozyme activities and protected C. gariepinus against bacterial infections where the lowest death was observed in the fish fed on the diet containing 1.5 g LBLE/kg feed. These findings showed that the fish fed with LBLE/kg diet improved their immune system, antioxidant and growth performance in addition to providing protection from A. hydrophila infection with the optimum dose of 1.80 g/kg diet., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Edwardsiella tarda is one of the most common causes of fish diseases that hinder aquaculture. Oxidative stress in farm animals can induce a number of pathological disorders, production and general animal welfare. The use of exogenous dietary nonenzymatic antioxidants such as alpha-lipoic acid (ALA) can stop a pro-oxidant state and thus appears to have the potential to modulate the immune system and protect fish from bacterial infection. Thus, this study investigates the stimulatory effect of dietary ALA on growth performance, antioxidant capacity, liver enzymes, immunity and protection of African catfish, Clarias gariepinus (B.), against an infection with E. tarda. Five isonitrogenous and isocaloric diets (400 g/kg of crude protein) containing ALA at doses of 0.0 (control), 500, 1000, 1500 or 2000 mg/kg diet were served to 300 juveniles of African catfish (mean weight = 8.2 ± 0.2 g) adequately thrice per day for 12 weeks. Thereafter, 0.1 mL of E. tarda (ATCC 15947; 1.0 × 10 8  CFU/mL) was intraperitoneally injected into 10 fish from each tank and was monitored for 14 days. The results showed that ALA-fortified diets significantly boosted the fish growth, feed consumption and utilization and feed conversion ratio but no did not affect fish survival rate. The highest final fish weight (g), weight growth (g) and weight gain (%) were all considerably higher in fish fed with ALA-fortified diets (p < 0.05), especially from 1000 to 200 mg/kg ALA than the control group. Also, an enhanced hemato-biochemical, antioxidant and immune indices were noticed in African catfish-fed ALA-enriched diets. In a dose-dependent order, the levels of haematological indices such Ht, Hb, RBCs, WBCs and platelets were markedly increased (p < 0.05). Additionally, fish fed with ALA-based diets showed substantial (p < 0.05) declines in aspartate and alanine aminotransferase values, with the lowest values being found in the 2000 mg/kg diet while control group had highest values. Further, African catfish fed the feed fortified with 2000 mg ALA/kg diet showed the highest levels of lysozyme, respiratory burst, proteases and esterase activities (p < 0.05). Following exposure of fish to E. tarda infection, a significant reduction in the mortality was obtained in African catfish fed with ALA-based diets, especially from 1500 to 2000 mg ALA/kg diet (3.3%); while fish fed with the control diet had highest mortality (86.7%). Therefore, diets supplemented with ALA evoked fish growth performance, antioxidants and nonspecific immunity of African catfish. Also, resistance of African catfish to E. Tarda infection were raised when fed ALA-fortified diets at optimum inclusion rate of 1300 mg ALA/kg diet., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Zika virus (ZIKV) poses a serious threat to the entire world. The rapid spread of ZIKV and recent outbreaks since 2007 have caused worldwide concern about the virus. Diagnosis is complicated because of the cross-reactivity of the virus with other viral antibodies. Currently, the virus is diagnosed by molecular techniques such as RT-PCR and IgM-linked enzyme immunoassays (MAC-ELISA). Recently, outbreaks and epidemics have been caused by ZIKV, and severe clinical symptoms and congenital malformations have also been associated with the virus. Although most ZIKV infections present with a subclinical or moderate flu-like course of illness, severe symptoms such as Guillain-Barre syndrome in adults and microcephaly in children of infected mothers have also been reported. Because there is no reliable cure for ZIKV and no vaccine is available, the public health response has focused primarily on preventing infection, particularly in pregnant women. A comprehensive approach is urgently needed to combat this infection and stop its spread and imminent threat. In view of this, this review aims to present the current structural and functional viewpoints, structure, etiology, clinical prognosis, and measures to prevent this transmission based on the literature and current knowledge. Moreover, we provide thorough description of the current understanding about ZIKV interaction with receptors, and a comparative examination of its similarities and differences with other viruses., Competing Interests: Declaration of Competing Interest All authors declare that there is no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Among primary liver cancers, hepatocellular carcinoma (HCC) is one of the most common forms and it has been categorized as the joint-fourth largest reason of cancer-related deaths globally. Different factors such as alcohol abuse, hepatitis B and C, viral infections, and fatty liver diseases are mainly related to the pathogenesis of HCC. In the current study, 1000 total various plant phytochemicals were docked to proteins involved in HCC. The compounds were docked to the active site amino acids of epidermal growth factor receptor and caspase-9 as receptor proteins in order to explore their inhibiting potential. The top five compounds against each receptor protein were explored as potential drug candidates on the basis of their binding affinity and root-mean square deviation values. The top two compounds against each protein were found to be liquoric acid (S-score -9.8 kcal/mol) and madecassic acid (S-score -9.3 kcal/mol) against EGFR, and limonin (S-score -10.5 kcal/mol) and obamegine (S-score -9.3 kcal/mol) against the caspase-9 protein. The selected phytochemicals were further assessed through drug scanning using Lipinski's rule of five to explore their molecular properties and druggability. According to the ADMET analysis, the selected phytochemicals were found to be non-toxic and non-carcinogenic. Finally, the molecular dynamics simulation study revealed that liquoric acid and limonin were stabilized within the binding pockets of EGFR and capase-9, respectively, and stayed firmly bound throughout the simulation. In light of the current findings, the phytochemicals reported in this study, especially liquoric acid and limonin, could be used as potential drugs for the treatment of HCC in the future.

Nanoviruses are plant multipartite viruses with a genome composed of six to eight circular single-stranded DNA segments. The distinct genome segments are encapsidated individually in icosahedral particles that measure ≈18 nm in diameter. Recent studies on the model species Faba bean necrotic stunt virus (FBNSV) revealed that complete sets of genomic segments rarely occur in infected plant cells and that the function encoded by a given viral segment can complement the others across neighbouring cells, presumably by translocation of the gene products through unknown molecular processes. This allows the viral genome to replicate, assemble into viral particles and infect anew, even with the distinct genome segments scattered in different cells. Here, we question the form under which the FBNSV genetic material propagates long distance within the vasculature of host plants and, in particular, whether viral particle assembly is required. Using structure-guided mutagenesis based on a 3.2 Å resolution cryogenic-electron-microscopy reconstruction of the FBNSV particles, we demonstrate that specific site-directed mutations preventing capsid formation systematically suppress FBNSV long-distance movement, and thus systemic infection of host plants, despite positive detection of the mutated coat protein when the corresponding segment is agroinfiltrated into plant leaves. These results strongly suggest that the viral genome does not propagate within the plant vascular system under the form of uncoated DNA molecules or DNA:coat-protein complexes, but rather moves long distance as assembled viral particles., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Trapani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mucor circinelloides serves as a model organism to investigate the lipid metabolism in oleaginous microorganisms. It is considered as an important producer of γ-linolenic acid (GLA) that has vital medicinal benefits. In this study, we used WJ11, a high lipid-producing strain of M. circinelloides (36% w/w lipid, cell dry weight, CDW), to examine the role in lipid accumulation of two mitochondrial malic enzyme (ME) genes malC and malD . The homologous overexpression of both malC and malD genes enhanced the total lipid content of WJ11 by 41.16 and 32.34%, respectively. In parallel, the total content of GLA was enhanced by 16.73 and 46.76% in malC and malD overexpressing strains, respectively, because of the elevation of total lipid content. The fact that GLA content was enhanced more in the strain with lower lipid content increase and vice versa, indicated that engineering of mitochondrial MEs altered the fatty acid profile. Our results reveal that mitochondrial ME plays an important role in lipid metabolism and suggest that future approaches may involve simultaneous overexpression of distinct ME genes to boost lipid accumulation even further., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fazili, Shah, Albeshr, Naz, Dar, Yang, Garre, Fazili, Bhat and Song.)

Background: Tumor necrosis factor interacting protein (TRAIP/TRIP) is an important cell-signaling molecule that prevents the TNF-induced-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation via direct interaction with TRAF 2 protein. TRAIP is a crucial downstream signaling molecule, implicated in several signaling pathways. Due to these multifunctional effects, TRAIP is more related to cellular mitosis, chromosome segregation, and DNA damage response. Tumor necrosis factor interacting protein is a downstream signaling molecule that contains a RING domain with E3 ubiquitin ligase activity at the N terminal side followed by coiled-coil and C terminal leucine zipper domain. Human TRAIP is constituted of 469 amino acids with 76% sequence similarity with the mouse TRAIP protein. Although, the main inhibitory function of TRAIP has been known for decades, however, in vitro interaction of TRAIPCC domain with RAP80 Zinc finger motif has not been reported yet. Besides, RAP80, the binding partner of TRAIPCC protein has been implicated in DNA damage response., Results: Our in vitro study shows that the TRAIP CC (64-166) associates with the RAP80 zinc finger of corresponding amino acid 490-584. However, TRAIP CCLZ (66-260) and TRAIP RINGCC (1 = 157) failed to interact with the RAP80 zinc finger of corresponding amino acid 490-584. The current study reinforces TRAIP CC (64-166) and RAP80 zinc finger of corresponding amino acid 490-584 associates to form a complex. Moreover, SDS PAGE arbitrated the homogeneity of RAP80 Zinc finger and TRAIP CC of corresponding amino acid 490-584 and 64-166, respectively., Conclusion: In vitro , a specific interaction was observed between the TRAIP CC (64-166) and the RAP80 zinc finger of the corresponding amino acid 490-584 and a specific binding area of the RAP80 zinc finger motif were investigated. The TRAIPCC region is required for the complex to bind to the RAP80-Zn finger motif. This strategy may be necessary for the RAP80 zinc finger activity to the TRAIP CC protein., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

The significance of biomaterials is well appreciated in nanotechnology, and its use has resulted in major advances in biomedical sciences. Although, currently, very little data is available on the clinical trial studies for treatment of neurological conditions, numerous promising advancements have been reported in drug delivery and regenerative therapies which can be applied in clinical practice. Among the commonly reported biomaterials in literature, the self-assembling peptides and hydrogels have been recognized as the most potential candidate for treatment of common neurological conditions such as Alzheimer's, Parkinson's, spinal cord injury, stroke and tumors. The hydrogels, specifically, offer advantages like flexibility and porosity, and mimics the properties of the extracellular matrix of the central nervous system. These factors make them an ideal scaffold for drug delivery through the blood-brain barrier and tissue regeneration (using stem cells). Thus, the use of biomaterials as suitable matrix for therapeutic purposes has emerged as a promising area of neurosciences. In this review, we describe the application of biomaterials, and the current advances, in treatment of statistically common neurological disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Khan, Rudrapal, Bhat, Ali, Alaidarous, Alshehri, Banwas, Ismail and Egbuna.)

Recently calcium homeostasis modulators (CALHMs) are identified as ATP release channels play crucial role in functioning of neurons including gustatory signaling and neuronal excitability. Pathologies of Alzheimer's disease and depression have been associated with the dysfunction of CALHMs. Recently, CALHMs has been emerged as an important therapeutic research particularly in neurobiological studies. CALHM1 is most extensively studied among CALHMs and is an ATP and ion channel that is activated by membrane depolarization or removal of extracellular Ca 2+ . Despite the emerged role of CALHM5 shown by an recently assembled data; however, the neuronal function remains obscure until the first Cryo-EM structure of CALHM5 was recently solved by various research group which acts as a template to study the hidden functional properties of the CALHM5 protein based on structure function mechanism. It provides insight in some of the different pathophysiological roles. CALHM5 structure showed an abnormally large pore channel structure assembled as an undecamer with four transmembrane helices (TM1-TM4), an N-terminal helix (NTH), an extracellular loop region and an intracellular C-terminal domain (CTD) that consists of three α-helices CH1-3. The TM1 and NTH were always poorly defined among all CALHMs; however, these regions were well defined in CALHM5 channel structure. In this context, this review will provide insight in structure, function and mechanism to understand its significant role in pathological diseases particularly in Alzheimer's disease. Moreover, it focuses on CALHM5 structure and recent associated properties based on Cryo-EM research., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The novel coronavirus disease (COVID-19) a global pandemic outbreak is an emerging new virus accountable for respiratory illness caused by SARS-CoV-2, originated in Wuhan city, Hubei province China, urgently calls to adopt prevention and intervention strategies. Several viral epidemics such as severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 to 2003 and H1N1 influenza in 2009 were reported since last two decades. Moreover, the Saudi Arabia was the epicenter for Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The CoVs are large family with single-stranded RNA viruses (+ssRNA). Genome sequence of 2019-nCoV, shows relatively different homology from other coronavirus subtypes, categorized in betacoronavirus and possibly found from strain of bats. The COVID-19 composed of exposed densely glycosylated spike protein (S) determines virus binding and infiltrate into host cells as well as initiate protective host immune response. Recently published reviews on the emerging SARS-CoV-2 have mainly focused on its structure, development of the outbreak, relevant precautions and management trials. Currently, there is an urgency of pharmacological intervention to combat this deadly infectious disease. Elucidation of molecular mechanism of COVID-19 becomes necessary. Based on the current literature and understanding, the aim of this review is to provide current genome structure, etiology, clinical prognosis as well as to explore the viral receptor binding together functional insight of SARS-CoV-2 infection (COVID-19) with treatment and preventive measures., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Pannexins, large non-gap junction super family exists in vertebrates, play multiple roles in different cellular functions through their ATP release. Panx1-mediated adenosine 5'-triphosphate (ATP) release plays a vital role in physiological and pathophysiological conditions and is known major extracellular molecule in purinergic signaling. To modulate their function in vivo, a proper regulation of channel is necessary. Post-translational modifications are considered to be some regulating mechanisms for PANX1, while PANX2, PANX3 have been uncharacterized to date. Through their significant evidences, PANXs exclude from gap junction and conduits ATP release and other cellular molecules from cells by various mechanisms. PANX1 is most extensive characterized and implicated in ATP signaling and inflammatory processes. Despite the constant advances, much significance of PANX1 in physiological processes remains elusive. Recently, various research groups along with our group have reported the Cryo-EM structure of Panx1 channel and uncovered the hidden functions in structure-function mechanism as well as to provide the clear understanding in physiological and pathophysiological roles. These research groups reported the novel heptameric structure with contains 4 transmembrane helices (TM), two extracellular loops and one intracellular loop with N and C terminus located at the intracellular side. In addition, the structure contains a large pore of which an inhibitor CBX act as a plug that blocking the passage of substrate. In this context, this review will present current mechanistic understanding in structure and function together with significant physiological roles particularly ATP release in health and disease. As such, this review emphasizes on recent functional properties associated with novel heptameric channel and demystifies channel-mediated ATP release function.

Exosomes are normal vesicles produced in the late endosomes of a cell. They are secreted by cells and play a role in cell-to-cell contact. They are an invaluable aid in cancer diagnosis as they include miRNA, proteins and lncRNAs. Depending on the function of these constituents in cancer, the expression of exosome constituents can be upregulated or downregulated in cancer. Exosomes provide high concentration and protective environment for their cargo, thereby making them superior targets for cancer diagnosis. It has recently been documented that exosomes modulate cell-cell connectivity by molecules included in the exosomes, leading to the maintenance of tissue homeostasis. In addition, exosomes released from cancer cells are implicated in the development of cancer. Data on the role of exosomes in cancer will thus enhance the effectiveness of new diagnostic and therapeutic approaches. In particular, exosomes are useful sources for biomarkers due to selective cargo loading and similarity to their parental cells. In this review, we summarize the recent findings to use exosomes as cancer biomarkers for early detection, diagnosis, and therapy selection., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The TRAIP interacting protein is known as a negative regulator of TNF-induced-nuclear factor, kappa-light-chain-enhancer of activated B cell (NF-κB) by direct interaction with the adaptor protein TRAF2, which inhibits the function of TRAF2 via the RINGCC domain protein. The TRAIP protein is composed of 469 amino acids with an N-terminal RING motif that is followed by a coiled coil (CC) and leucine zipper domain. TRAIP proteins are critical in programmed cell death, cell proliferation and differentiation, and embryonic development. The critical functions of TRAIP together with the molecular inhibitory mechanism effect of TRAIP have been reported by two different studies and have opened up new research into the field of TRAF biology. In this study, we designed different constructs of the Leucine zipper domain to find the over -expressed construct for further studies. We successfully cloned the C-terminal TRAIP containing the leucine zipper domain. In addition, we have over-expressed and purified the TRAIP LZ for their biochemical characterization., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Published by Elsevier B.V. on behalf of King Saud University.)

TNF receptor proteins were primarily recognized as adaptor proteins that ligate with the tumor necrosis factor receptor (TNFR)-associated factor (TNFR) family to execute various signaling pathways. However, recent studies showed that they act as a signal-transducing molecules and are reported to have a functional role as a Toll/interleukin-1 receptor family member. Seven members of this family have been identified to date. Among TNF receptor family, TRAF7 does not share a common TRAF domain homology. The tumor necrosis factor receptor associated factor (TRAF) domain comprises of about 230 amino acid motif at the C-terminal region that has the capability to bind TNFR and execute different downstream signaling pathways. Moreover, N-terminal RING and ZINC finger constituted by the tumor necrosis factor associated protein 2 and tumor necrosis factor associated protein 6 are critical and execute various downstream signaling events. TRAF proteins have emerged as critical regulators that provide the cellular response to stress and lead to cell death. Nuclear factor kappa beta (NF-KB) and c-Jun N-terminal kinases (JNK) pathways are activated through tumor necrosis factor associated protein 2, tumor necrosis factor associated protein 5 and tumor necrosis factor associated protein 6 members. TRAF proteins in pathogenesis were observed from their abnormal expression in diseased tissue and in normal tissue, suggesting its important role in physiological processes. Recently, unique specificity of TRAF4 for glycoprotein Ibβ (GPIbβ) and glycoprotein VI (GPVI) in human platelets has been reported. The multifunctional effects of TRAIP (TNF) interacting protein in many cellular signaling pathways emerged as very important signaling molecule. Furthermore, the new insights into the structure of TRAF members along with new studies involved in health and disease prompted to explore their role particularly the TNF receptor associated proteins with novel inhibitor protein TRAIP (TNF) interacting protein and human diseases associated with it. As such, this review emphasis on tumor necrosis factor receptor associated proteins, present their current understanding with novel inhibitor protein TRAIP (TNF) interacting protein., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

TRAF-interacting protein (TRAIP), a negative regulator of TNF-induced-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, inhibits adaptor protein TRAF2 by direct interaction and is critical in apoptosis, cell proliferation, antiviral response, and embryonic development. Although the critical function of TRAIP in NF-κB signaling is well-known, the molecular inhibitory mechanism of TRAIP remains unclear. We found that the TRAIP coiled-coil domain altered its stoichiometry between dimer and trimer in a concentration-dependent manner. Additionally, the TRAIP RING domain induced even higher-ordered assembly, which was necessary for interacting with the TRAF-N domain of TRAF2 but not TRAF1. Characterization of the TRAF-N domains of TRAF1 and TRAF2, the tentative TRAIP-binding region of TRAFs, suggested the molecular basis of the inhibitory effect of TRAIP on TRAF2 in NF-κB signaling.

Background: Grx6 is a yeast Golgi/endoplasmic reticulum protein involved in iron-sulfur binding that belongs to monothiol glutaredoxin-protein family. Grx6 has been biochemically characterized previously. Grx6 contains a conserved cysteine residue (Cys-136). Depending on the active-site sequences, Grxs can be classified to classic dithiol Grxs with a CXXC motif known as classes II and monothiol Grxs with a CXXS motif known as classes I, and Grx6 belongs to the class I with a CSYS motif., Results: Our results showed how the loop between the N-terminal and C-terminal can affect the stability. When Grx6 was incubated with FeSO 4 ·7H 2 O and (NH 4 ) 2 Fe(SO 4 ) 2 ·6H 2 O, a disulfide bond was formed between the cysteine 136 and glutathione, and the concentration of dimer and tetramer was increased. The results presented various levels of stability of Grx6 with mutant and deleted amino acids. We also highlighted the difference between the monomer and dimer forms of the Grx6, in addition to comparison of the Fe-S cluster positions among holo forms of poplar Grx-C1, human Grx2 and Saccharomyces cerevisiae Grx6., Conclusions: In this paper, we used a combination of spectroscopic and proteomic techniques to analyse the sequence and to determine the affected mutations and deletions in the stability of Grx6. Our results have increased the knowledge about the differences between monomer and dimer structures in cellular processes and proteins whose roles and functions depend on YCA1 in yeast., Competing Interests: Not applicable Not applicable The authors declare that they have no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This study was designed to evaluate the protective effect of ethanol extract (SEL001) isolated from a potent probiotic strain Lactobacillus sakei proBio-65 on imiquimod (IMQ)-induced psoriasis-like skin inflammation in a mouse model. Histopathological and histomorphometrical changes in the ear and dorsal skin tissues were observed under hematoxylin and eosin stain for general histopathological architectures or Masson's trichrome stain for collagen fibers. The expression profile of psoriasis-associated specific genes was determined using Real-Time PCR analysis. As a result, topical application of IMQ resulted in a significant increase of mean total and epithelial (epidermis) thicknesses, the number of inflammatory cells infiltrated in the dermis, and the decrease of dermis collagen fiber occupied regions in the ear tissues of IMQ and IMQ plus vaseline treated groups when compared to the intact control group. A significant increase of epithelial thickness and number of inflammatory cells infiltrated in the dermis of dorsal skin tissues were also noticed in IMQ and IMQ plus vaseline treated groups as compared to the intact control group, suggesting classic IMQ-induced hypersensitive psoriasis. IMQ-induced hypersensitive psoriasis related histopathological changes to the ear and dorsal skin tissues were significantly inhibited by the treatment of a standard drug clobetasol and SEL001. Further, mRNA expression analysis indicated a significant increase in gene expression levels of pro-inflammatory cytokines, including IL-19, IL-17A, and IL-23 in IMQ and IMQ plus vaseline treated groups than that of the control. Clobetasol and SEL001 treated groups resulted in a lower gene expression level of IL-19, IL-17A, and IL-23 as compared to IMQ and IMQ plus vaseline treated groups. These results enforce that SEL001 could be a novel treatment for psoriasis and an alternative to other drugs that pose a number of side effects on the skin.

TNF-receptor associated factor (TRAF) proteins are key adaptor molecules containing E3 ubiquitin ligase activity that play a critical role in immune cell signaling. TRAF1 is a unique family of TRAF lacking the N-terminal RING finger domain. TRAF1 is an important scaffold protein that participates in TNFR2 signaling in T cells as a negative or positive regulator via direct interaction with TRAF2, which has recently been identified as a pro-apoptotic regulator in neuronal cell death. Here, we report the first crystal structure of the TRAF1 TRAF domain containing both the TRAF-N coiled-coil domain and the TRAF-C domain. Our structure reveals both similarities and differences with other TRAF family members, which may be functionally relevant to TRAFs. We also found that the TRAF-N coiled-coil domain of TRAF1 is critical for the trimer formation and stability of the protein. Finally, we found that conserved surface residues on the TRAF1 TRAF domain that might be binding hot spots that are critical for interaction with signaling molecules.

Inflammatory caspases, such as caspase-1, which is critical for the innate immune response, are activated upon the formation of a molecular complex called the inflammasome. The inflammasome is composed of three proteins, the Nod-like receptor (NLRP, NLRC or AIM2), apoptosis associated speck-loke protein containing a caspase-recruitment domain (ASC), and caspase-1. ASC is an adaptor molecule that contains an N-terminal PYD domain and a C-terminal CARD domain for interaction with other proteins. Upon activation, the N-terminal PYD of ASC homotypically interacts with the PYD domain of the Nod-like receptor, while its C-terminal CARD homotypically interacts with the CARD domain of caspase-1. PYD only protein 1 (POP1) negatively regulates inflammatory response by blocking the formation of the inflammasome. POP1 directly binds to ASC via a PYD:PYD interaction, thereby preventing ASC recruitment to Nod-like receptor NLRPs. POP1-mediated regulation of inflammation is of great biological importance. Here, we report the crystal structure of human POP1 and speculate about the inhibitory mechanism of POP1-mediated inflammasome formation based on the current structure., (Copyright © 2015 Elsevier Inc. All rights reserved.)