National Centre for Cell Science

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Macrophages are one of the principal immune effector cells that play essential roles as secretory, phagocytic, and antigen-presenting cells in the immune system. In this study, we address the issue of cytotoxicity and immunogenic effects of gold nanoparticles on RAW264.7 macrophage cells. The cytotoxicity of gold nanoparticles has been correlated with a detailed study of their endocytotic uptake using various microscopy tools such as atomic force microscopy (AFM), confocal-laser-scanning microscopy (CFLSM), and transmission electron microscopy (TEM). Our findings suggest that Au(0) nanoparticles are not cytotoxic, reduce the production of reactive oxygen and nitrite species, and do not elicit secretion of proinflammatory cytokines TNF-alpha and IL1-beta, making them suitable candidates for nanomedicine. AFM measurements suggest that gold nanoparticles are internalized inside the cell via a mechanism involving pinocytosis, while CFLSM and TEM studies indicate their internalization in lysosomal bodies arranged in perinuclear fashion. Our studies thus underline the noncytotoxic, nonimmunogenic, and biocompatible properties of gold nanoparticles with the potential for application in nanoimmunology, nanomedicine, and nanobiotechnology.

. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

Natural killer (NK) cells are innate immune cells that show strong cytolytic function against physiologically stressed cells such as tumor cells and virus-infected cells. NK cells show a broad array of tissue distribution and phenotypic variability. NK cells express several activating and inhibitory receptors that recognize the altered expression of proteins on target cells and control the cytolytic function. NK cells have been used in several clinical trials to control tumor growth. However, the results are encouraging only in hematological malignancies but not very promising in solid tumors. Increasing evidence suggests that tumor microenvironment regulate the phenotype and function of NK cells. In this review, we discussed the NK cell phenotypes and its effector function and impact of the tumor microenvironment on effector and cytolytic function of NK cells. We also summarized various NK cell-based immunotherapeutic strategies used in the past and the possibilities to improve the function of NK cell for the better clinical outcome.

The cellular mechanisms underlying the increasing aggressiveness associated with ovarian cancer progression are poorly understood. Coupled with a lack of identification of specific markers that could aid early diagnoses, the disease becomes a major cause of cancer-related mortality in women. Here we present direct evidence that the aggressiveness of human ovarian cancer may be a result of transformation and dysfunction of stem cells in the ovary. A single tumorigenic clone was isolated among a mixed population of cells derived from the ascites of a patient with advanced ovarian cancer. During the course of the study, yet another clone underwent spontaneous transformation in culture, providing a model of disease progression. Both the transformed clones possess stem cell-like characteristics and differentiate to grow in an anchorage-independent manner in vitro as spheroids, although further maturation and tissue-specific differentiation was arrested. Significantly, tumors established from these clones in animal models are similar to those in the human disease in their histopathology and cell architecture. Furthermore, the tumorigenic clones, even on serial transplantation continue to establish tumors, thereby confirming their identity as tumor stem cells. These findings suggest that: (a) stem cell transformation can be the underlying cause of ovarian cancer and (b) continuing stochastic events of stem and progenitor cell transformation define the increasing aggression that is characteristically associated with the disease.

The transcriptional repressors Snail and Slug contribute to cancer progression by mediating epithelial-mesenchymal transition (EMT), which results in tumor cell invasion and metastases. We extend this current understanding to demonstrate their involvement in the development of resistance to radiation and paclitaxel. The process is orchestrated through the acquisition of a novel subset of gene targets that is repressed under conditions of stress, effectively inactivating p53-mediated apoptosis, while another subset of targets continues to mediate EMT. Repressive activities are complemented by a concurrent derepression of specific genes resulting in the acquisition of stem cell-like characteristics. Such cells are bestowed with three critical capabilities, namely EMT, resistance to p53-mediated apoptosis, and a self-renewal program, that together define the functionality and survival of metastatic cancer stem cells. EMT provides a mechanism of escape to a new, less adverse niche; resistance to apoptosis ensures cell survival in conditions of stress in the primary tumor; whereas acquisition of "stemness" ensures generation of the critical tumor mass required for progression of micrometastases to macrometastases. Our findings, besides achieving considerable expansion of the inventory of direct genes targets, more importantly demonstrate that such elegant cooperative modulation of gene regulation mediated by Snail and Slug is critical for a cancer cell to acquire stem cell characteristics toward resisting radiotherapy- or chemotherapy-mediated cellular stress, and this may be a determinative aspect of aggressive cancer metastases.

Summary: Complement protein C3 is a central molecule in the complement system whose activation is essential for all the important functions performed by this system. After four decades of research it is now well established that C3 functions like a double‐edged sword: on the one hand it promotes phagocytosis, supports local inflammatory responses against pathogens, and instructs the adaptive immune response to select the appropriate antigens for a humoral response; on the other hand its unregulated activation leads to host cell damage. In addition, its interactions with the proteins of foreign pathogens may provide a mechanism by which these microorganisms evade complement attack. Therefore, a clear knowledge of the molecule and its interactions at the molecular level not only may allow the rational design of molecular adjuvants but may also lead to the development of complement inhibitors and new therapeutic agents against infectious diseases. A.S. is a Wellcome Trust Overseas Senior Research Fellow in Biomedical Science in India. This research was supported by National Institutes of Health grants AI 30040, GM 56698, HL28220, and AI 48487.

Neuroprotection is a proactive approach to safeguarding the nervous system, including the brain, spinal cord, and peripheral nerves, by preventing or limiting damage to nerve cells and other components. It primarily defends the central nervous system against injury from acute and progressive neurodegenerative disorders. Oxidative stress, an imbalance between the body's natural defense mechanisms and the generation of reactive oxygen species, is crucial in developing neurological disorders. Due to its high metabolic rate and oxygen consumption, the brain is particularly vulnerable to oxidative stress. Excessive ROS damages the essential biomolecules, leading to cellular malfunction and neurodegeneration. Several neurological disorders, including Alzheimer's, Parkinson's, Amyotrophic lateral sclerosis, multiple sclerosis, and ischemic stroke, are associated with oxidative stress. Understanding the impact of oxidative stress in these conditions is crucial for developing new treatment methods. Researchers are exploring using antioxidants and other molecules to mitigate oxidative stress, aiming to prevent or slow down the progression of brain diseases. By understanding the intricate interplay between oxidative stress and neurological disorders, scientists hope to pave the way for innovative therapeutic and preventive approaches, ultimately improving individuals' living standards.

After the 1918 flu pandemic, the world is again facing a similar situation. However, the advancement in medical science has made it possible to identify that the novel infectious agent is from the coronavirus family. Rapid genome sequencing by various groups helped in identifying the structure and function of the virus, its immunogenicity in diverse populations, and potential preventive measures. Coronavirus attacks the respiratory system, causing pneumonia and lymphopenia in infected individuals. Viral components like spike and nucleocapsid proteins trigger an immune response in the host to eliminate the virus. These viral antigens can be either recognized by the B cells or presented by MHC complexes to the T cells, resulting in antibody production, increased cytokine secretion, and cytolytic activity in the acute phase of infection. Genetic polymorphism in MHC enables it to present some of the T cell epitopes very well over the other MHC alleles. The association of MHC alleles and its downregulated expression has been correlated with disease severity against influenza and coronaviruses. Studies have reported that infected individuals can, after recovery, induce strong protective responses by generating a memory T-cell pool against SARS-CoV and MERS-CoV. These memory T cells were not persistent in the long term and, upon reactivation, caused local damage due to cross-reactivity. So far, the reports suggest that SARS-CoV-2, which is highly contagious, shows related symptoms in three different stages and develops an exhaustive T-cell pool at higher loads of viral infection. As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. A classical immunotherapy of convalescent plasma transfusion from recovered patients has also been initiated for the neutralization of viremia in terminally ill COVID-19 patients. Due to the limitations of plasma transfusion, researchers are now focusing on developing neutralizing antibodies against virus particles along with immuno-modulation of cytokines like IL-6, Type I interferons (IFNs), and TNF-α that could help in combating the infection. This review highlights the similarities of the coronaviruses that caused SARS and MERS to the novel SARS-CoV-2 in relation to their pathogenicity and immunogenicity and also focuses on various treatment strategies that could be employed for curing COVID-19.

Although it is well established that reactive oxygen intermediates mediate the NF-κB activation induced by most agents, how H2O2 activates this transcription factor is not well understood. We found that treatment of human myeloid KBM-5 cells with H2O2 activated NF-κB in a dose- and time-dependent manner much as tumor necrosis factor (TNF) did but unlike TNF, H2O2 had no effect on IκBα degradation. Unexpectedly, however, like TNF-induced activation, H2O2-induced NF-κB activation was blocked by the calpain inhibitor N-Ac-Leu-Leu-norleucinal, suggesting that a proteosomal pathway was involved. Although H2O2 activated IκBα kinase, it did not induce the serine phosphorylation of IκBα. Like TNF, H2O2 induced the serine phosphorylation of the p65 subunit of NF-κB, leading to its nuclear translocation. We found that H2O2 induced the tyrosine phosphorylation of IκBα, which is needed for NF-κB activation. We present several lines of evidence to suggest that the Syk protein-tyrosine kinase is involved in H2O2-induced NF-κB activation. First, H2O2 activated Syk in KBM-5 cells; second, H2O2 failed to activate NF-κB in cells that do not express Syk protein; third, overexpression of Syk increased H2O2-induced NF-κB activation; and fourth, reduction of Syk transcription using small interfering RNA inhibited H2O2-induced NF-κB activation. We also showed that Syk induced the tyrosine phosphorylation of IκBα, which caused the dissociation, phosphorylation, and nuclear translocation of p65. Thus, overall, our results demonstrate that H2O2 induces NF-κB activation, not through serine phosphorylation or degradation of IκBα, but through Syk-mediated tyrosine phosphorylation of IκBα Although it is well established that reactive oxygen intermediates mediate the NF-κB activation induced by most agents, how H2O2 activates this transcription factor is not well understood. We found that treatment of human myeloid KBM-5 cells with H2O2 activated NF-κB in a dose- and time-dependent manner much as tumor necrosis factor (TNF) did but unlike TNF, H2O2 had no effect on IκBα degradation. Unexpectedly, however, like TNF-induced activation, H2O2-induced NF-κB activation was blocked by the calpain inhibitor N-Ac-Leu-Leu-norleucinal, suggesting that a proteosomal pathway was involved. Although H2O2 activated IκBα kinase, it did not induce the serine phosphorylation of IκBα. Like TNF, H2O2 induced the serine phosphorylation of the p65 subunit of NF-κB, leading to its nuclear translocation. We found that H2O2 induced the tyrosine phosphorylation of IκBα, which is needed for NF-κB activation. We present several lines of evidence to suggest that the Syk protein-tyrosine kinase is involved in H2O2-induced NF-κB activation. First, H2O2 activated Syk in KBM-5 cells; second, H2O2 failed to activate NF-κB in cells that do not express Syk protein; third, overexpression of Syk increased H2O2-induced NF-κB activation; and fourth, reduction of Syk transcription using small interfering RNA inhibited H2O2-induced NF-κB activation. We also showed that Syk induced the tyrosine phosphorylation of IκBα, which caused the dissociation, phosphorylation, and nuclear translocation of p65. Thus, overall, our results demonstrate that H2O2 induces NF-κB activation, not through serine phosphorylation or degradation of IκBα, but through Syk-mediated tyrosine phosphorylation of IκBα Nuclear factor-κB (NF-κB) 1The abbreviations used are: NF-κB, nuclear factor kappa B; IκB, inhibitory subunit of NF-κB; IKK, IκBα kinase; TNF, tumor necrosis factor; Syk, spleen tyrosine kinase; p56lck, lymphocyte-specific protein-tyrosine kinase; EMSA, electrophoretic mobility shift assay; ALLN, N-acetyl-leucyl-leucyl-norleucinal; siRNA, small interfering RNA. is a transcription factor consisting of a group of five proteins, namely c-Rel, RelA (p65), Rel B, NF-κB1 (p50 and p105), and NF-κB2 (p52) (1Ghosh S. Karin M. Cell. 2002; 109: S81-S96Google Scholar). In the resting state, NF-κB is sequestered in the cytoplasm through its tight association with specific inhibitory proteins, called inhibitors of NF-κB (IκB), belonging to a gene family consisting of IκBα, IκBβ, IκBϵ, IκBγ, Bcl-3, p100, and p105 (1Ghosh S. Karin M. Cell. 2002; 109: S81-S96Google Scholar). On activation by agents such as TNF, IκBα is phosphorylated at serine residues 32 and 36, ubiquitinated at lysine residues 21 and 22, and degraded through the proteosomal pathway, thus exposing the nuclear localization signals on the p50-p65 heterodimer. Then p65 undergoes phosphorylation, leading to nuclear translocation and binding to a specific sequence in DNA, which in turn results in gene transcription. The phosphorylation of IκBα is catalyzed by IκBα kinase (IKK), which consists of IKK-α, IKK-β, and IKK-γ (also called NF-κB essential modulator (NEMO)) (1Ghosh S. Karin M. Cell. 2002; 109: S81-S96Google Scholar). Gene deletion studies have established that IKK-β is essential for NF-κB activation by TNF (2Li Z.W. Chu W. Hu Y. Delhase M. Deerinck T. Ellisman M. Johnson R. Karin M. J. Exp. Med. 1999; 189: 1839-1845Google Scholar, 3Li Q. Estepa G. Memet S. Israel A. Verma I.M. Genes Dev. 2000; 14: 1729-1733Crossref Google Scholar, 4Li Q. Antwerp D.V. Mercurio F. Lee K.F. Verma I.M. Science. 1999; 284: 321-325Google Scholar). IKK-α deletion, however, has no effect on NF-κB activation by most agents. Which kinase induces the phosphorylation of p65 is controversial, but protein kinase A, casein kinase II, IKK-α, and IKK-β have all been implicated (5Hayashi T. Sekine T. Okamoto T. J. Biol. Chem. 1993; 268: 26790-26795Google Scholar, 6Zhong H. SuYang H. Erdjument-Bromage H. Tempst P. Ghosh S. Cell. 1997; 89: 413-424Google Scholar, 7Zhong H. Voll R.E. Ghosh S. Mol. Cell. 1998; 1: 661-671Google Scholar, 8Wang D. Westerheide S.D. Hanson J.L. Baldwin Jr., A.S. J. Biol. Chem. 2000; 275: 32592-32597Google Scholar, 9Sakurai H. Chiba H. Miyoshi H. Sugita T. Toriumi W. J. Biol. Chem. 1999; 274: 30353-30356Google Scholar, 10Sizemore N. Lerner N. Dombrowski N. Sakurai H. Stark G.R. J. Biol. Chem. 2002; 277: 3863-3869Google Scholar). The phosphorylation of p65 at serine 529 has been shown to be required for the TNF-induced transcriptional activity of NF-κB (11Wang D. Baldwin Jr., A.S. J. Biol. Chem. 1998; 273: 29411-29416Google Scholar). NF-κB is activated by a wide variety of agents, including all 18 members of the TNF superfamily, interleukin-1, interleukin-17, interleukin-18, lipopolysaccharide, H2O2, ceramide, phorbol esters, growth factors, UV, X-rays, and γ-radiation (12Garg A. Aggarwal B.B. Leukemia. 2002; 16: 1053-1068Google Scholar). Whether all these agents activate NF-κB through the same pathway as described above is not clear. Certain agents activate NF-κB not through serine phosphorylation but through tyrosine phosphorylation of IκBα: nerve growth factor, erythropoietin, pervanadate, hypoxia, and silica (13Bui N.T. Livolsi A. Peyron J.F. Prehn J.H. J. Cell Biol. 2001; 152: 753-764Google Scholar, 14Digicaylioglu M. Lipton S.A. Nature. 2001; 412: 641-647Google Scholar, 15Imbert V. Rupec R.A. Livolsi A. Pahl H.L. Traenckner E.B. Mueller-Dieckmann C. Farahifar D. Rossi B. Auberger P. Baeuerle P.A. Peyron J.F. Cell. 1996; 86: 787-798Google Scholar, 16Singh S. Darnay B.G. Aggarwal B.B. J. Biol. Chem. 1996; 271: 31049-31054Google Scholar, 17Kang J.L. Pack I.S. Hong S.M. Lee H.S. Castranova V. Toxicol. Appl. Pharmacol. 2000; 169: 59-65Google Scholar, 18Koong A.C. Chen E.Y. Giaccia A.J. Cancer Res. 1994; 54: 1425-1430Google Scholar). The tyrosine phosphorylation of IκBα by most agents does not lead to IκBα degradation. Pervanadate-induced NF-κB activation, however, leads to tyrosine phosphorylation and degradation of IκBα (19Mukhopadhyay A. Manna S.K. Aggarwal B.B. J. Biol. Chem. 2000; 275: 8549-8555Google Scholar). Surprisingly, UV-C-induced NF-κB activation is mediated through the degradation of IκBα that involves phosphorylation of neither serine nor the tyrosine residue of IκBα (20Li N. Karin M. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 13012-13017Google Scholar). Pervanadate-induced tyrosine phosphorylation of IκBα blocks the TNF-induced serine phosphorylation of IκBα and NF-κB activation (16Singh S. Darnay B.G. Aggarwal B.B. J. Biol. Chem. 1996; 271: 31049-31054Google Scholar, 21Singh S. Aggarwal B.B. J. Biol. Chem. 1995; 270: 10631-10639Google Scholar), indicating potential stereochemical hindrance. NF-κB activation of most agents has been shown to require the generation of reactive oxygen intermediates, in studies that used either reactive oxygen intermediate quenchers, such as N-acetylcysteine, or antioxidant enzymes, such as glutathione peroxidase, superoxide dismutase, γ-glutamylcysteine synthetase, and thioredoxin (22Staal F.J. Roederer M. Herzenberg L.A. Herzenberg L.A. Proc. Natl. Acad. Sci. U. S. A. 1990; 87: 9943-9947Google Scholar, 23Kretz-Remy C. Mehlen P. Mirault M.E. Arrigo A.P. J. Cell Biol. 1996; 133: 1083-1093Google Scholar, 24Schreck R. Rieber P. Baeuerle P.A. EMBO J. 1991; 10: 2247-2258Google Scholar, 25Giri D.K. Aggarwal B.B. J. Biol. Chem. 1998; 273: 14008-14014Google Scholar, 26Manna S.K. Zhang H.J. Yan T. Oberley L.W. Aggarwal B.B. J. Biol. Chem. 1998; 273: 13245-13254Google Scholar, 27Manna S.K. Kuo M.T. Aggarwal B.B. Oncogene. 1999; 18: 4371-4382Google Scholar, 28Shrivastava A. Aggarwal B.B. Antioxid Redox Signal. 1999; 1: 181-191Google Scholar, 29Matthews J.R. Wakasugi N. Virelizier J.L. Yodoi J. Hay R.T. Nucleic Acids Res. 1992; 20: 3821-3830Google Scholar). Additionally, there are reports that H2O2 activates NF-κB (23Kretz-Remy C. Mehlen P. Mirault M.E. Arrigo A.P. J. Cell Biol. 1996; 133: 1083-1093Google Scholar, 24Schreck R. Rieber P. Baeuerle P.A. EMBO J. 1991; 10: 2247-2258Google Scholar, 30Meyer M. Schreck R. Baeuerle P.A. EMBO J. 1993; 12: 2005-2015Google Scholar). Although it has been shown that H2O2-induced NF-κB is blocked by N-acetylcysteine (24Schreck R. Rieber P. Baeuerle P.A. EMBO J. 1991; 10: 2247-2258Google Scholar), how H2O2 activates NF-κB is not fully understood (31Livolsi A. Busuttil V. Imbert V. Abraham R.T. Peyron J.F. Eur. J. Biochem. 2001; 268: 1508-1515Google Scholar, 32Schoonbroodt S. Ferreira V. Best-Belpomme M. Boelaert J.R. J. Immunol. 2000; 164: Scholar, H. T. S. H. 2002; Scholar). In the present the of H2O2-induced NF-κB activation. We found that H2O2-induced NF-κB activation degradation of IκBα. H2O2 activated Syk protein-tyrosine kinase, which in turn induced tyrosine phosphorylation of IκBα, leading to NF-κB activation. human to with a specific activity of was by and H2O2 was and was Cell and by and that the serine of p65 was as described M.T. M. A.J. Nature. 2000; Scholar), was by C. D. of was used for of of human Syk or human Syk and to which the and of The sequence used was are in are in and is Cell KBM-5 is myeloid with The lines and human cells human cells and cells the and Cell cells with the gene by of The of these cells has been A. Cell. 1992; Scholar). KBM-5 cells in with and cells in with and NF-κB activation, as described A. Aggarwal B.B. 2000; Scholar). nuclear cells with NF-κB of protein with of the human NF-κB binding for at and the was on was used to the of binding of NF-κB to the The of binding was also by with the nuclear cells with either or p65 of NF-κB for at the was by and as The and by a using the of protein in cytoplasm or nuclear S. Aggarwal B.B. J. Immunol. 2001; cells and by the to with and by The of the was using a and IκBα was by a described S.K. A. Aggarwal B.B. J. Immunol. 2000; Scholar). cytoplasm was with IKK-α, by treatment with protein a the with and in kinase of and of the was at for the was by with for the protein was on the was and the by the of IKK-α and IKK-β in of the protein was on to a and with either or Syk the activity of protein-tyrosine kinase Syk induced by H2O2, with and the in kinase using the as the cells with A.C. N. S. Aggarwal B.B. for with H2O2 for and in the and The kinase protein was using by protein the with the and in a kinase and of and at the with for to and the and by a using The tyrosine phosphorylation of IκBα by Syk was also by using in the kinase as described and using Nuclear of p65 NF-κB by effect of H2O2 on the nuclear translocation of p65 was by the as described A. C. M. 1992; Scholar). cells on a by using a with and with of in blocked with for and with p65 or IκBα at at the with at for and for with for with and a using and for on in and of in was with of was using protein for at with and in for and in and the of Syk protein-tyrosine kinase in the H2O2-induced NF-κB activation, cells either with small interfering or with of in was in of and and with of was to the cells and for was and for cells used to the of Syk protein by NF-κB activity by EMSA, and Syk activity by the kinase as described In this the effect of H2O2 on NF-κB activation, IκBα phosphorylation, IκBα p65 phosphorylation, and nuclear and the of protein-tyrosine kinase Syk in H2O2-induced NF-κB activation. NF-κB activation by TNF is well used TNF as a for most by and the treatment of cells with H2O2 for had no effect on was TNF of NF-κB in a and the effect of H2O2 on the activation of NF-κB, KBM-5 cells with of H2O2 for or TNF for Nuclear for of NF-κB activation by H2O2 and TNF induced NF-κB activation in a manner in KBM-5 cells activation with H2O2 at NF-κB was activated by agents in a time-dependent manner TNF induced NF-κB activation and activation for H2O2-induced NF-κB activation at at and at The TNF-induced NF-κB activation was with H2O2 it was Thus, H2O2 induced NF-κB activation did The and in the of activation suggest that the of NF-κB activation by H2O2 is that of NF-κB is a of proteins, of protein NF-κB that to a specific sequence in (1Ghosh S. Karin M. Cell. 2002; 109: S81-S96Google Scholar). that the by in cells was NF-κB, nuclear cells with to either the or the p65 subunit of the to a thus suggesting that the of and p65 nor had NF-κB caused of the and a of NF-κB did not NF-κB binding NF-κB TNF-induced NF-κB activation the degradation of IκBα S. Karin M. Cell. 2002; 109: S81-S96Google Scholar). Whether H2O2-induced NF-κB activation is also mediated through IκBα degradation was cells with TNF or H2O2 for the the and for IκBα on using TNF induced IκBα degradation and IκBα was at H2O2 did not induce IκBα degradation at TNF but induces phosphorylation of 32 and of IκBα S. Karin M. Cell. 2002; 109: S81-S96Google Scholar). H2O2 induces serine phosphorylation of IκBα. the phosphorylated IκBα, blocked degradation of IκBα using the inhibitor A.C. N. S. Aggarwal B.B. Scholar). using showed that TNF induced the phosphorylation of IκBα but H2O2 had no effect on the serine phosphorylation of IκBα. NF-κB by TNF and blocked not TNF-induced NF-κB activation, but also H2O2-induced NF-κB activation IκBα phosphorylation and degradation are in TNF-induced NF-κB activation. and of the effect of TNF and H2O2 on translocation and phosphorylation of p65 by TNF and H2O2 induced nuclear translocation of p65 in a time-dependent On TNF p65 nuclear translocation TNF treatment and In the of H2O2, p65 translocation was induced at and TNF and H2O2 induced the phosphorylation of p65 in a time-dependent but the of H2O2-induced phosphorylation of p65 was that for TNF showed that in p65 was in the TNF and H2O2 induced translocation of p65 the H2O2-induced phosphorylation and translocation of p65 to the with TNF-induced IκBα our results that H2O2-induced NF-κB activation is not mediated through the phosphorylation and degradation of IκBα, H2O2 activate has been shown that is required not for TNF-induced phosphorylation of IκBα but also for the phosphorylation of p65 H. Chiba H. Miyoshi H. Sugita T. Toriumi W. J. Biol. Chem. 1999; 274: 30353-30356Google Scholar, 10Sizemore N. Lerner N. Dombrowski N. Sakurai H. Stark G.R. J. Biol. Chem. 2002; 277: 3863-3869Google Scholar). in kinase using as the showed that TNF and H2O2 activated as as TNF but activation H2O2-induced activation however, that induced by TNF nor H2O2 had effect on the of either IKK-α or IKK-β results suggest that H2O2 activated but had no effect on the serine phosphorylation of IκBα. NF-κB in the of Syk in H2O2-induced NF-κB activation, used cells to A. Cell. 1992; and Syk protein S. S. T. Cell 1998; 10: Scholar). that cells Syk protein but cells or no Syk The was specific as it did not protein in cells TNF activated NF-κB in and cells and induced IκBα degradation in the lines The of TNF-induced NF-κB activation, however, was in cells in cells and the of activation was also In H2O2 activated NF-κB in cells but not in cells indicating essential of Syk protein in H2O2-induced activation. We also the of H2O2 to activate NF-κB in human and which be activated for Syk and cells with H2O2 for the nuclear and for NF-κB activation by for Syk activation. We found that H2O2 failed to activate Syk and this with the of activation of NF-κB in and Whether H2O2 activate NF-κB in cells was this cells for the with H2O2 and for NF-κB activation by and IκBα degradation by shown in H2O2 induced NF-κB activation in cells and this was with the degradation and of IκBα. results with a S. Ferreira V. Best-Belpomme M. Boelaert J.R. J. Immunol. 2000; 164: but that in human NF-κB in cells have been shown to and Syk protein-tyrosine A. Cell. 1992; Scholar). have shown that is required for and NF-κB activation S.K. Aggarwal B.B. J. Biol. Chem. 2000; 275: Scholar, S.K. Aggarwal B.B. J. Immunol. 2000; 164: Scholar). of cells had been that H2O2 activated NF-κB in cells but not in cells had been IκBα phosphorylation was in either of the lines In was not required for H2O2-induced NF-κB activation or for IκBα of Syk in but in and cells with H2O2 for the with and to using H2O2-induced tyrosine phosphorylation of Syk in but not in cells of IκBα in our and have shown that agents activate NF-κB through tyrosine phosphorylation it does not lead to the degradation of IκBα (13Bui N.T. Livolsi A. Peyron J.F. Prehn J.H. J. Cell Biol. 2001; 152: 753-764Google Scholar, 14Digicaylioglu M. Lipton S.A. Nature. 2001; 412: 641-647Google Scholar, 15Imbert V. Rupec R.A. Livolsi A. Pahl H.L. Traenckner E.B. Mueller-Dieckmann C. Farahifar D. Rossi B. Auberger P. Baeuerle P.A. Peyron J.F. Cell. 1996; 86: 787-798Google Scholar, 16Singh S. Darnay B.G. Aggarwal B.B. J. Biol. Chem. 1996; 271: 31049-31054Google Scholar, 17Kang J.L. Pack I.S. Hong S.M. Lee H.S. Castranova V. Toxicol. Appl. Pharmacol. 2000; 169: 59-65Google Scholar, 18Koong A.C. Chen E.Y. Giaccia A.J. Cancer Res. 1994; 54: 1425-1430Google Scholar). H2O2 did not induce IκBα H2O2 induces tyrosine phosphorylation of IκBα. cells with H2O2 tyrosine phosphorylation of IκBα is the of of cells with tyrosine phosphorylation of IκBα results suggest that H2O2 induced tyrosine phosphorylation of IκBα by of Syk tyrosine Syk of the of Syk-mediated phosphorylation of IκBα, the in kinase using as the We found that Syk IκBα, and this phosphorylation was by treatment the Syk-mediated tyrosine phosphorylation of IκBα, the in kinase using as the and The IκBα was by using and results suggest that Syk protein-tyrosine kinase IκBα on tyrosine of IκBα p65 serine phosphorylation leads to the degradation of IκBα, tyrosine phosphorylation does not (13Bui N.T. Livolsi A. Peyron J.F. Prehn J.H. J. Cell Biol. 2001; 152: 753-764Google Scholar, 14Digicaylioglu M. Lipton S.A. Nature. 2001; 412: 641-647Google Scholar, 15Imbert V. Rupec R.A. Livolsi A. Pahl H.L. Traenckner E.B. Mueller-Dieckmann C. Farahifar D. Rossi B. Auberger P. Baeuerle P.A. Peyron J.F. Cell. 1996; 86: 787-798Google Scholar, 16Singh S. Darnay B.G. Aggarwal B.B. J. Biol. Chem. 1996; 271: 31049-31054Google Scholar, 17Kang J.L. Pack I.S. Hong S.M. Lee H.S. Castranova V. Toxicol. Appl. Pharmacol. 2000; 169: 59-65Google Scholar, 18Koong A.C. Chen E.Y. Giaccia A.J. Cancer Res. 1994; 54: 1425-1430Google Scholar). Whether H2O2-induced tyrosine phosphorylation of IκBα was for the of p65 was cells with TNF or with H2O2 and for IκBα by TNF induced the degradation of IκBα in the and the translocation of p65 to the TNF also induced the of p65 IκBα In the p65 was the degradation of IκBα We to that H2O2 did not induce of p65 IκBα H2O2 induced a of IκBα and IκBα be in neither nor p65 showed that p65 and IκBα in the of cells The cells with TNF IκBα in the and p65 was to the in these Although H2O2 induced p65 translocation the IκBα in the results suggest that H2O2 induced translocation of p65 of Syk H2O2-induced NF-κB and of the of Syk protein-tyrosine kinase in H2O2-induced NF-κB activation, the cells with the Syk shown in these cells showed in of Syk protein H2O2-induced NF-κB activation and in the IκBα tyrosine phosphorylation the these results suggest that Syk protein-tyrosine kinase mediate H2O2-induced NF-κB through the tyrosine phosphorylation of IκBα. of Syk by H2O2-induced NF-κB and of also used to Syk T. 2002; 20: Scholar). and H2O2-induced NF-κB activation and IκBα tyrosine shown in the of Syk protein H2O2-induced NF-κB activation and tyrosine phosphorylation of IκBα as with the results suggest that Syk in NF-κB activation induced by using inhibitors and antioxidant enzymes, it has been well established that oxygen are involved in NF-κB activation by most agents. Additionally, that H2O2 activate NF-κB has been for a but the has We demonstrate in the present that H2O2 activates NF-κB the IκBα and its serine it induced tyrosine phosphorylation of activated IKK-α and Syk kinase, and this activation of Syk kinase to be for tyrosine phosphorylation of IκBα and for NF-κB activation. TNF and H2O2 activated NF-κB, but the of NF-κB activation was with TNF that with results in that the of NF-κB activation by TNF are that of Although reactive oxygen intermediates has been implicated in TNF-induced NF-κB activation R. B. W. Baeuerle P.A. J. Exp. Med. 1992; Scholar, H.J. B. J. Biol. Chem. 2001; Scholar), this not be for NF-κB activation. The in also be to the of TNF-induced activation H2O2 activity is We have in that the of NF-κB activation by H2O2 is that of TNF induced IκBα degradation but H2O2 did agents are also to activate NF-κB IκBα including pervanadate, hypoxia, erythropoietin, and nerve growth factor (13Bui N.T. Livolsi A. Peyron J.F. Prehn J.H. J. Cell Biol. 2001; 152: 753-764Google Scholar, 14Digicaylioglu M. Lipton S.A. Nature. 2001; 412: 641-647Google Scholar, 15Imbert V. Rupec R.A. Livolsi A. Pahl H.L. Traenckner E.B. Mueller-Dieckmann C. Farahifar D. Rossi B. Auberger P. Baeuerle P.A. Peyron J.F. Cell. 1996; 86: 787-798Google Scholar, 16Singh S. Darnay B.G. Aggarwal B.B. J. Biol. Chem. 1996; 271: 31049-31054Google Scholar, 17Kang J.L. Pack I.S. Hong S.M. Lee H.S. Castranova V. Toxicol. Appl. Pharmacol. 2000; 169: 59-65Google Scholar, 18Koong A.C. Chen E.Y. Giaccia A.J. Cancer Res. 1994; 54: 1425-1430Google Scholar). results with F. A. Biol. Med. 2001; and S.A. Biochem. 1998; but S. Ferreira V. Best-Belpomme M. Boelaert J.R. J. Immunol. 2000; 164: Scholar), showed that H2O2 induces IκBα degradation in Whether these are to is not clear. We used lines and myeloid cells and found results also suggest unlike TNF, H2O2 does not induce serine phosphorylation of IκBα. S. Ferreira V. Best-Belpomme M. Boelaert J.R. J. Immunol. 2000; 164: also showed that phosphorylation of serine 32 and of IκBα is not required for NF-κB activation by was the for TNF, H2O2-induced NF-κB activation was by ALLN, a proteosomal H2O2-induced NF-κB activation is not clear. The has been implicated in the degradation of IκBα and in the of p105 and is that H2O2-induced NF-κB activation through the of degradation of IκBα or of NF-κB The inhibitors and have also been shown to H2O2-induced NF-κB activation IκBα, or in cells 1998; Scholar). results suggest the of factor in H2O2-induced NF-κB activation. results also demonstrate that H2O2 did not induce serine phosphorylation of IκBα, it did activate IKK, phosphorylated p65 at serine residue and p65 to the it was that p65 H. Chiba H. Miyoshi H. Sugita T. Toriumi W. J. Biol. Chem. 1999; 274: 30353-30356Google Scholar, 10Sizemore N. Lerner N. Dombrowski N. Sakurai H. Stark G.R. J. Biol. Chem. 2002; 277: 3863-3869Google Scholar). it is that H2O2-induced is needed not for the phosphorylation of IκBα but for the phosphorylation of p65. results are in with a by H. T. S. H. 2002; Scholar), showed that H2O2 activate and this activation is essential for NF-κB activation. H2O2-induced activates NF-κB, however, was not by these results S. Ferreira V. Best-Belpomme M. Boelaert J.R. J. Immunol. 2000; 164: Scholar), showed of activation of by results that H2O2 induces tyrosine phosphorylation of IκBα. results are in with reports by Livolsi (31Livolsi A. Busuttil V. Imbert V. Abraham R.T. Peyron J.F. Eur. J. Biochem. 2001; 268: 1508-1515Google and S. Ferreira V. Best-Belpomme M. Boelaert J.R. J. Immunol. 2000; 164: Scholar). kinase induces the tyrosine phosphorylation of IκBα, however, is not clear. results evidence that Syk protein kinase a in this First, H2O2 activated Syk in KBM-5 cells; H2O2 failed to activate NF-κB in cells that do not express Syk protein; third, overexpression of Syk increased H2O2-induced NF-κB activation; and fourth, reduction of Syk transcription using inhibited H2O2-induced NF-κB activation. We also showed that Syk induced the tyrosine phosphorylation of IκBα, which caused the dissociation, phosphorylation, and nuclear translocation of p65. Lee R.A. J. Biol. Chem. 2002; 277: showed that H2O2-induced phosphorylation of IκBα through in H2O2 has been shown to activate Syk H. Biochem. Res. 1998; Scholar), a kinase to be in and and We found that cells that do not express Syk, such as of failed to activate NF-κB on treatment with V. J. Biol. Chem. 1998; 273: showed that in human cells or human TNF activate NF-κB but H2O2 The of H2O2 to activate NF-κB in these cells have been of a of of Syk kinase in these it has been shown that H2O2 activate Proc. Natl. Acad. Sci. U. S. A. 1995; Scholar). Although has been implicated in the NF-κB activation by and by S.K. Aggarwal B.B. J. Biol. Chem. 2000; 275: Scholar, S.K. Aggarwal B.B. J. Immunol. 2000; 164: Scholar), our results that H2O2 does not induce NF-κB activation through activation of as cells did not to H2O2 for NF-κB activation. We found that in all the of IκBα was degraded and the p65 was to the In in cells IκBα was phosphorylated but not to p65 in the a of the p65 was to the results thus suggest that H2O2-induced NF-κB activation through a that of In our that H2O2 induces a Syk kinase, which in turn induces tyrosine phosphorylation of IκBα. IκBα induces the p65 NF-κB leading to p65 phosphorylation and nuclear translocation.

Cytokines regulate immune responses essential for maintaining immune homeostasis, as deregulated cytokine signaling can lead to detrimental outcomes, including inflammatory disorders. The antioxidants emerge as promising therapeutic agents because they mitigate oxidative stress and modulate inflammatory pathways. Antioxidants can potentially ameliorate inflammation-related disorders by counteracting excessive cytokine-mediated inflammatory responses. A comprehensive understanding of cytokine-mediated inflammatory pathways and the interplay with antioxidants is paramount for developing natural therapeutic agents targeting inflammation-related disorders and helping to improve clinical outcomes and enhance the quality of life for patients. Among these antioxidants, curcumin, vitamin C, vitamin D, propolis, allicin, and cinnamaldehyde have garnered attention for their anti-inflammatory properties and potential therapeutic benefits. This review highlights the interrelationship between cytokines-mediated disorders in various diseases and therapeutic approaches involving antioxidants. • Cytokines, produced by immune cells, are pivotal players in many health conditions. • The imbalance of cytokines results in an excessive immune response. • Antioxidants provide therapeutic benefits in inflammatory conditions. • Antioxidants combined with radiotherapy can be an effective therapeutic option.

Breast cancer is a multifactorial disease and driven by aberrant regulation of cell signaling pathways due to the acquisition of genetic and epigenetic changes. An array of growth factors and their receptors is involved in cancer development and metastasis. Receptor Tyrosine Kinases (RTKs) constitute a class of receptors that play important role in cancer progression. RTKs are cell surface receptors with specialized structural and biological features which respond to environmental cues by initiating appropriate signaling cascades in tumor cells. RTKs are known to regulate various downstream signaling pathways such as MAPK, PI3K/Akt and JAK/STAT. These pathways have a pivotal role in the regulation of cancer stemness, angiogenesis and metastasis. These pathways are also imperative for a reciprocal interaction of tumor and stromal cells. Multi-faceted role of RTKs renders them amenable to therapy in breast cancer. However, structural mutations, gene amplification and alternate pathway activation pose challenges to anti-RTK therapy.

Inflammation appears to be a necessity for both metastasis and elimination of tumor cells. IL-17, a proinflammatory cytokine produced by Th17 cells, contributes to both the processes by playing a dual role in the antitumor immunity. On one hand, IL-17 promotes an antitumor cytotoxic T cell response leading to tumor regression. On the other hand, by facilitating angiogenesis and egress of tumor cells from the primary focus, IL-17 promotes tumor growth. Thus, the therapeutic application that uses IL-17 needs to be refined by minimizing its protumor functions.

Wnt signaling is one of the central mechanisms regulating tissue morphogenesis during embryogenesis and repair. The pivot of this signaling cascade is the Wnt ligand, which binds to receptors belonging to the Frizzled family or the ROR1/ROR2 and RYK family. This interaction governs the downstream signaling cascade (canonical/non-canonical), ultimately extending its effect on the cellular cytoskeleton, transcriptional control of proliferation and differentiation, and organelle dynamics. Anomalous Wnt signaling has been associated with several cancers, the most prominent ones being colorectal, breast, lung, oral, cervical, and hematopoietic malignancies. It extends its effect on tumorigenesis by modulating the tumor microenvironment via fine crosstalk between transformed cells and infiltrating immune cells, such as leukocytes. This review is an attempt to highlight the latest developments in the understanding of Wnt signaling in the context of tumors and their microenvironment. A dynamic process known as immunoediting governs the fate of tumor progression based on the correlation of various signaling pathways in the tumor microenvironment and immune cells. Cancer cells also undergo a series of mutations in the tumor suppressor gene, which favors tumorigenesis. Wnt signaling, and its crosstalk with various immune cells, has both negative as well as positive effects on tumor progression. On one hand, it helps in the maintenance and renewal of the leucocytes. On the other hand, it promotes immune tolerance, limiting the antitumor response. Wnt signaling also plays a role in epithelial-mesenchymal transition (EMT), thereby promoting the maintenance of Cancer Stem Cells (CSCs). Furthermore, we have summarized the ongoing strategies used to target aberrant Wnt signaling as a novel therapeutic intervention to combat various cancers and their limitations.

There has been significant progress in the biological synthesis of nanomaterials. However, the molecular mechanism of synthesis of such bio-nanomaterials remains largely unknown. Here, we report the extracellular synthesis of crystalline silver nanoparticles (AgNPs) by using Morganella sp., and show molecular evidence of silver resistance by elucidating the synthesis mechanism. The AgNPs were 20+/-5 nm in diameter and were highly stable at room temperature. The kinetics of AgNPs formation was investigated. Detectable particles were formed after an hour of reaction, and their production remained exponential up to 18 h, and saturated at 24 h. Morganella sp. was found to be highly resistant to silver cations and was able to grow in the presence of more than 0.5 mM AgNO(3). Three gene homologues viz. silE, silP and silS were identified in silver-resistant Morganella sp. The homologue of silE from Morganella sp. showed 99 % nucleotide sequence similarity with the previously reported gene, silE, which encodes a periplasmic silver-binding protein. The homologues of silP and silS were also highly similar to previously reported sequences. Similar activity was totally absent in closely related Escherichia coli; this suggests that a unique mechanism of extracellular AgNPs synthesis is associated with silver-resistant Morganella sp. The molecular mechanism of silver resistance and its gene products might have a key role to play in the overall synthesis process of AgNPs by Morganella sp. An understanding of such biochemical mechanisms at the molecular level might help in developing an ecologically friendly and cost-effective protocol for microbial AgNPs synthesis.

Currently, a small number of diseases, particularly cardiovascular (CVDs), oncologic (ODs), neurodegenerative (NDDs), chronic respiratory diseases, as well as diabetes, form a severe burden to most of the countries worldwide. Hence, there is an urgent need for development of efficient diagnostic tools, particularly those enabling reliable detection of diseases, at their early stages, preferably using non-invasive approaches. Breath analysis is a non-invasive approach relying only on the characterisation of volatile composition of the exhaled breath (EB) that in turn reflects the volatile composition of the bloodstream and airways and therefore the status and condition of the whole organism metabolism. Advanced sampling procedures (solid-phase and needle traps microextraction) coupled with modern analytical technologies (proton transfer reaction mass spectrometry, selected ion flow tube mass spectrometry, ion mobility spectrometry, e-noses, etc.) allow the characterisation of EB composition to an unprecedented level. However, a key challenge in EB analysis is the proper statistical analysis and interpretation of the large and heterogeneous datasets obtained from EB research. There is no standard statistical framework/protocol yet available in literature that can be used for EB data analysis towards discovery of biomarkers for use in a typical clinical setup. Nevertheless, EB analysis has immense potential towards development of biomarkers for the early disease diagnosis of diseases.

BACKGROUND: Cellular miRNAs play an important role in the regulation of gene expression in eukaryotes. Recently, miRNAs have also been shown to be able to target and inhibit viral gene expression. Computational predictions revealed earlier that the HIV-1 genome includes regions that may be potentially targeted by human miRNAs. Here we report the functionality of predicted miR-29a target site in the HIV-1 nef gene. RESULTS: We find that the human miRNAs hsa-miR-29a and 29b are expressed in human peripheral blood mononuclear cells. Expression of a luciferase reporter bearing the nef miR-29a target site was decreased compared to the luciferase construct without the target site. Locked nucleic acid modified anti-miRNAs targeted against hsa-miR-29a and 29b specifically reversed the inhibitory effect mediated by cellular miRNAs on the target site. Ectopic expression of the miRNA results in repression of the target Nef protein and reduction of virus levels. CONCLUSION: Our results show that the cellular miRNA hsa-miR29a downregulates the expression of Nef protein and interferes with HIV-1 replication.

Angiogenesis is the hallmark of cancer, and development of aggressiveness of primary tumor depends on de novo angiogenesis. Here, using multiple in vitro and in vivo models, we report that osteopontin (OPN) triggers vascular endothelial growth factor (VEGF)-dependent tumor progression and angiogenesis by activating breast tumor kinase (Brk)/nuclear factor-inducing kinase/nuclear factor-kappaB (NF-kappaB)/activating transcription factor-4 (ATF-4) signaling cascades through autocrine and paracrine mechanisms in breast cancer system. Our results revealed that both exogenous and tumor-derived OPN play significant roles in VEGF-dependent tumor angiogenesis. Clinical specimen analysis showed that OPN and VEGF expressions correlate with levels of neuropilin-1, Brk, NF-kappaB, and ATF-4 in different grades of breast cancer. Consequently, OPN plays essential role in two key aspects of tumor progression: VEGF expression by tumor cells and VEGF-stimulated neovascularization. Thus, targeting OPN and its regulated signaling network could be a novel strategy to block tumor angiogenesis and may develop an effective therapeutic approach for the management of breast cancer.

Antileishmanial immune response is shown to be host genotype dependent so that some inbred strains of mouse are susceptible while others are resistant. The resistance is conferred by T-helper type-1 (Th1) cells while the susceptibility is conferred by Th2 cells. Th1 cells secrete IL-2 and IFN-gamma but Th2 cells secrete IL-4, IL-5 and IL-10. It has been shown that IFN-gamma activates macrophages to express iNOS2, the enzyme catalyzing the formation of nitric oxide. Nitric oxide kills the intracellular amastigotes. In contrast, Th2 immune response limits the action of Th1 functions via IL-10 and IL-4, which deactivate macrophages helping intracellular parasite growth and disease progression. Being a parasite, Leishmania ensures its own survival by modulating host immune system either by inducing immunosuppression or by promoting pro-parasitic host functions. A detailed knowledge of this host-parasite interaction would help in designing prophylactic and therapeutic strategies against this infection.

Novel species of fungi described in this study include those from various countries as follows: Antarctica: Cadophora antarctica from soil. Australia : Alfaria dandenongensis on Cyperaceae , Amphosoma persooniae on Persoonia sp., Anungitea nullicana on Eucalyptus sp., Bagadiella eucalypti on Eucalyptus globulus , Castanediella eucalyptigena on Eucalyptus sp., Cercospora dianellicola on Dianella sp., Cladoriella kinglakensis on Eucalyptus regnans , Cladoriella xanthorrhoeae (incl. Cladoriellaceae fam. nov. and Cladoriellales ord. nov.) on Xanthorrhoea sp., Cochlearomyces eucalypti (incl. Cochlearomyces gen. nov. and Cochlearomycetaceae fam. nov.) on Eucalyptus obliqua , Codinaea lambertiae on Lambertia formosa , Diaporthe obtusifoliae on Acacia obtusifolia , Didymella acaciae on Acacia melanoxylon , Dothidea eucalypti on Eucalyptus dalrympleana , Fitzroyomyces cyperi (incl. Fitzroyomyces gen. nov.) on Cyperaceae , Murramarangomyces corymbiae (incl. Murramarangomyces gen. nov., Murramarangomycetaceae fam. nov. and Murramarangomycetales ord. nov.) on Corymbia maculata , Neoanungitea eucalypti (incl. Neoanungitea gen. nov.) on Eucalyptus obliqua , Neoconiothyrium persooniae (incl. Neoconiothyrium gen. nov.) on Persoonia laurina subsp. laurina , Neocrinula lambertiae (incl. Neocrinulaceae fam. nov.) on Lambertia sp., Ochroconis podocarpi on Podocarpus grayae , Paraphysalospora eucalypti (incl. Paraphysalospora gen. nov.) on Eucalyptus sieberi , Pararamichloridium livistonae (incl. Pararamichloridium gen. nov., Pararamichloridiaceae fam. nov. and Pararamichloridiales ord. nov.) on Livistona sp., Pestalotiopsis dianellae on Dianella sp., Phaeosphaeria gahniae on Gahnia aspera , Phlogicylindrium tereticornis on Eucalyptus tereticornis , Pleopassalora acaciae on Acacia obliquinervia , Pseudodactylaria xanthorrhoeae (incl. Pseudodactylaria gen. nov., Pseudodactylariaceae fam. nov. and Pseudodactylariales ord. nov.) on Xanthorrhoea sp., Pseudosporidesmium lambertiae (incl. Pseudosporidesmiaceae fam. nov.) on Lambertia formosa , Saccharata acaciae on Acacia sp., Saccharata epacridis on Epacris sp., Saccharata hakeigena on Hakea sericea , Seiridium persooniae on Persoonia sp., Semifissispora tooloomensis on Eucalyptus dunnii , Stagonospora lomandrae on Lomandra longifolia , Stagonospora victoriana on Poaceae , Subramaniomyces podocarpi on Podocarpus elatus , Sympoventuria melaleucae on Melaleuca sp., Sympoventuria regnans on Eucalyptus regnans , Trichomerium eucalypti on Eucalyptus tereticornis , Vermiculariopsiella eucalypticola on Eucalyptus dalrympleana , Verrucoconiothyrium acaciae on Acacia falciformis , Xenopassalora petrophiles (incl. Xenopassalora gen. nov.) on Petrophile sp., Zasmidium dasypogonis on Dasypogon sp., Zasmidium gahniicola on Gahnia sieberiana . Brazil : Achaetomium lippiae on Lippia gracilis , Cyathus isometricus on decaying wood , Geastrum caririense on soil, Lycoperdon demoulinii (incl. Lycoperdon subg. Arenicola ) on soil, Megatomentella cristata (incl. Megatomentella gen. nov.) on unidentified plant, Mutinus verrucosus on soil, Paraopeba schefflerae (incl. Paraopeba gen. nov.) on Schefflera morototoni , Phyllosticta catimbauensis on Mandevilla catimbauensis , Pseudocercospora angularis on Prunus persica , Pseudophialophora sorghi on Sorghum bicolor , Spumula piptadeniae on Piptadenia paniculata . Bulgaria : Yarrowia parophonii from gut of Parophonus hirsutulus . Croatia : Pyrenopeziza velebitica on Lonicera borbasiana . Cyprus : Peziza halophila on coastal dunes Czech Republic : Aspergillus contaminans from human fingernail. Ecuador : Cuphophyllus yacurensis on forest soil, Ganoderma podocarpense on fallen tree trunk. England : Pilidium anglicum (incl. Chaetomellales ord. nov.) on Eucalyptus sp. France : Planamyces parisiensis (incl. Planamyces gen. nov.) on wood inside a house. French Guiana : Lactifluus ceraceus on soil. Germany : Talaromyces musae on Musa sp. India : Hyalocladosporiella cannae on Canna indica , Nothophoma raii from soil. Italy : Setophaeosphaeria citri on Citrus reticulata , Yuccamyces citri on Citrus limon . Japan : Glutinomyces brunneus (incl. Glutinomyces gen. nov.) from roots of Quercus sp. Netherlands (all from soil): Collariella hilkhuijsenii , Fusarium petersiae , Gamsia kooimaniorum , Paracremonium binnewijzendii , Phaeoisaria annesophieae , Plectosphaerella niemeijerarum , Striaticonidium deklijnearum , Talaromyces annesophieae , Umbelopsis wiegerinckiae , Vandijckella johannae (incl. Vandijckella gen. nov. and Vandijckellaceae fam. nov.), Verhulstia trisororum (incl. Verhulstia gen. nov.). New Zealand : Lasiosphaeria similisorbina on decorticated wood. Papua New Guinea : Pseudosubramaniomyces gen. nov. (based on Pseudosubramaniomyces fusisaprophyticus comb. nov.). Slovakia : Hemileucoglossum pusillum on soil. South Africa : Tygervalleyomyces podocarpi</jats:ital