Scientific publications

Group 3 innate lymphoid cells mediate early protective immunity against tuberculosis


Amanda Ardain, William G. C. Horsnell, Racquel Domingo-Gonzalez, Shibali Das, Samuel Kazer, Nicole Howard, Alveera Singh, Mushtaq Ahmed, Shepherd Nhamoyebonde, Javier Rangel-Moreno, Paul Ogongo, Lan Lu, Duran Ramsuran, Maria de la Luz Garcia-Hernandez, Tyler K. Ulland, Matthew Darby, Eugene Park, Farina Karim, Laura Melocchi, Rajhmun Madansein, Kaylesh Jay Dullabh, Micah Dunlap, Nancy Marin-Agudelo, Takashi Ebihara, Thumbi Ndung’u, Deepak Kaushal, Alexander Pym, Jay Kolls, Adrie Steyn, Joaquín Zúñiga, Wayne Yokoyama, Alex Shalek, Henrik Kløverpris, Marco Colonna, Alasdair Leslie, Shabaana Khader

DOI https://doi.org/10.1038/s41586-019-1276-2
Scientific Field Life & Health Sciences
Fellow Dr William Horsnell
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Tuberculosis is the leading cause of death by an infectious disease worldwide1. However, the involvement of innate lymphoid cells (ILCs) in immune responses to infection with Mycobacterium tuberculosis (Mtb) is unknown. Here we show that circulating subsets of ILCs are depleted from the blood of participants with pulmonary tuberculosis and restored upon treatment. Tuberculosis increased accumulation of ILC subsets in the human lung, coinciding with a robust transcriptional response to infection, including a role in orchestrating the recruitment of immune subsets. Using mouse models, we show that group 3 ILCs (ILC3s) accumulated rapidly in Mtb-infected lungs and coincided with the accumulation of alveolar macrophages. Notably, mice that lacked ILC3s exhibited a reduction in the accumulation of early alveolar macrophages and decreased Mtb control. We show that the C-X-C motif chemokine receptor 5 (CXCR5)–C-X-C motif chemokine ligand 13 (CXCL13) axis is involved in Mtb control, as infection upregulates CXCR5 on circulating ILC3s and increases plasma levels of its ligand, CXCL13, in humans. Moreover, interleukin-23-dependent expansion of ILC3s in mice and production of interleukin-17 and interleukin-22 were found to be critical inducers of lung CXCL13, early innate immunity and the formation of protective lymphoid follicles within granulomas. Thus, we demonstrate an early protective role for ILC3s in immunity to Mtb infection.


Luminescence Properties of Self-Aggregating Tb III-DOTA-Functionalized Calix[4]arenes


Florian Mayer, Sriram Tiruvadi Krishnan, Daniel T Schühle, Svetlana V Eliseeva, Stéphane Petoud, Éva Tóth, Kristina Djanashvili

DOI 10.3389/fchem.2018.00001
Scientific Field Life & Health Sciences
Fellow Dr Kristina Djanashvili
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Self-aggregating calix[4]arenes carrying four DOTA ligands on the upper rim for stable complexation of paramagnetic Gd III-ions have already been proposed as MRI probes. In this work, we investigate the luminescence properties of Tb III-DOTA-calix[4]arene-4OPr containing four propyl-groups and compare them with those of the analog substituted with a phthalimide chromophore (Tb III-DOTA-calix[4]arene-3OPr-OPhth). We show that, given its four aromatic rings, the calix[4]arene core acts as an effective sensitizer of Tb-centered luminescence. Substituents on the lower rim can modulate the aggregation behavior, which in turn determines the luminescence properties of the compounds. In solid state, the quantum yield of the phthalimide derivative is almost three times as high as that of the propyl-functionalized analog demonstrating a beneficial role of the chromophore on Tb-luminescence. In solution, however, the effect of the phthalimide group vanishes, which we attribute to the large distance between the chromophore and the lanthanide, situated on the opposite rims of the calix[4]arene. Both quantum yields and luminescence lifetimes show clear concentration dependence in solution, related to the strong impact of aggregation on the luminescence behavior. We also evidence the variability in the values of the critical micelle concentration depending on the experimental technique. Such luminescent calix[4]arene platforms accommodating stable lanthanide complexes can be considered valuable building blocks for the design of dual MR/optical imaging probes.


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This paper suggests a new interpretation of the tale of Lisabetta da Messina (Decameron IV 5) in the light of a fact which has thus far been disregarded by scholars: namely, that in both medieval culture, and its basis in Roman law, an individual cannot have more than one grave. In case of dismemberment, the burial place is considered to be the place where the head is interred. Therefore, the pot of basil in Boccaccio's tale is Lorenzo's tomb, and Lisabetta beheads her dead lover in order to be able to perform suitable funeral rites. Taking this into account, her behaviour as well as other aspects of the tale take on new meaning.


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Bruxelles et le livre: regards sur cinq siècles d'histoire (XVIe-XXe siècle)


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In more general terms, many mediaeval authors-and not only theologians used the distinction between God's ordered and absolute power (potentia Dei absoluta and ordinata) to emphasize how, on the one hand, in an 'orderly' way, the realm of nature reflects God's freedom of choice, leading to the existence of a radically contingent order of creation; but also how, on the other hand, in terms of divine absoluteness and in the economy of salvation, God is never bound in his action, which is truly inscrutable and lies above morality. 1 The extensive scholarship on this distinction clearly demonstrates how such a question represented a real 'problem' for mediaeval thinkers rather than just a simple theory. 2 I am limited to mentioning here that the doctrine of God's power comes to the fore with a much different significance in various historical epochs.


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This review article discusses the active constituents and potential of two menthol mint oils, Mentha piperita (MPEO) and Mentha arvensis (MAEO), as natural sources for botanical pesticides. The biological activities of these menthol mint oils, which can be useful in agriculture, have been broadly researched, especially toward phytotoxic microorganisms. To a lesser extent, the insecticidal and herbicidal activities of mint EOs have also been studied. It is apparent that the prospect of using menthol mint oils in agriculture is increasing in popularity. A number of investigations showed that the in vitro efficacy of MPEO and MAEO, as well as that of their main constituent, menthol, is pronounced. The results of in vitro research are useful for choosing EOs for further investigations. However, it is clear that in situ experiments are crucial and should be more extensively developed. At the same time, known techniques are to be applied to this area and new methods should be worked out, aiming at the improvement of EOs’ pesticidal efficacy and cost-effectiveness, for future implementation in agricultural pest control.


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Follicle‐stimulating hormone (FSH) has been used in inconclusive clinical trials for male idiopathic infertility in the past. FSH is sometimes prescribed empirically for male idiopathic infertility, showing some improvement in sperm parameters in about half of the patients. In this opinion article, we briefly analyze the pathophysiological evidences in favor of a more aggressive approach in planning future studies on pharmacological FSH use in male infertility, in analogy with the FSH use for multiple follicular growth in women undergoing ovarian stimulation for assisted reproduction. There is sufficient evidence that spermatogenesis does not run at its top in the primate and that some extra FSH can stimulate spermatogenesis over its baseline. Existing data suggest that the pharmacological regimens applied so far were insufficient, both in dosage and in duration, to elicit this response in about half of the patients. A paradigm change is needed now: We should move away from the classical, endocrinological approach, which simply applied the substitutive, therapeutic regimen used in hypogonadotropic hypogonadism, toward testing a ‘testicular hyperstimulation’ scheme for a time sufficient to cover more than only one spermatogenic cycle, a concept to be verified in an appropriately controlled, prospective, randomized clinical trial.


LAPTM4B gene polymorphism augments the risk of cancer: Evidence from an updated meta‐analysis


Mohammad Hashemi, Gholamreza Bahari, Farhad Tabasi, Jarosław Markowski, Andrzej Małecki, Saeid Ghavami, Marek J. Łos

DOI https://doi.org/10.1111/jcmm.13896
Scientific Field Life & Health Sciences
Fellow Prof. Marek Los
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Lysosome‐associated protein transmembrane‐4 beta (LAPTM4B) has two alleles named as LAPTM4B*1 and LAPTM4B*2 (GenBank No. AY219176 and AY219177). Allele *1 has a single copy of a 19‐bp sequence in the 5` untranslated region (5`UTR), but allele *2 contains tandem repeats of 19‐bp sequence. LAPTM4B gene is located on long chromosome 8 (8q22.1) and contains seven exons that encodes two isoforms of tetratransmembrane proteins, LAPTM4B‐24 and LAPTM4B‐35, with molecular weights of 25 kDa and 35 kDa respectively. The LAPTM4B‐35′s primary structure is formed by 317 amino acid residues, and LAPTM4B‐24 comprised 226 amino acids. LAPTM4B, an integral membrane protein, contains several lysosomal‐targeting motifs at the C terminus and colocalizes with late endosomal and lysosomal markers. LAPTM4B is a proto‐oncogene, which becomes up‐regulated in various cancers. Preceding studies have examined the possible link between LAPTM4B polymorphism and susceptibility to several cancers,but the findings are still inconsistent. Hence, the present meta‐analysis was designed to investigate the impact of LAPTM4B polymorphism on risk of cancer.


Association of PDCD6 polymorphisms with the risk of cancer: Evidence from a meta-analysis


Mohammad Hashemi, Gholamreza Bahari, Jarosław Markowski, Andrzej Małecki, Marek J. Łos, Saeid Ghavami

DOI https://doi.org/10.18632/oncotarget.25324
Scientific Field Life & Health Sciences
Fellow Prof. Marek Los
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This study was designed to evaluate the relationship between Programmed cell death protein 6 (PDCD6) polymorphisms and cancer susceptibility. The online databases were searched for relevant case-control studies published up to November 2017. Review Manage (RevMan) 5.3 was used to conduct the statistical analysis. The pooled odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate the strength of association. Overall, our results indicate that PDCD6 rs3756712 T>G polymorphism was significantly associated with decreased risk of cancer under codominant (OR = 0.82, 95%CI = 0.70–0.96, p = 0.01, TG vs TT; OR = 0.53, 95%CI = 0.39-0.72, p < 0.0001, GG vs TT), dominant (OR = 0.76, 95%CI = 0.66-0.89, p = 0.0004, TG+GG vs TT), recessive (OR = 0.57, 95%CI = 0.43-0.78, p = 0.0003, GG vs TT+TG), and allele (OR = 0.76, 95%CI = 0.67–0.86, p < 0.00001, G vs T) genetic model. The finding did not support an association between rs4957014 T>G polymorphism of PDCD6, and different cancers risk.


Structure and properties of slow-resorbing nanofibers obtained by (co-axial) electrospinning as tissue scaffolds in regenerative medicine


Andrzej Hudecki​, Joanna Gola, Saeid Ghavami, Magdalena Skonieczna, Jarosław Markowski, Wirginia Likus, Magdalena Lewandowska, Wojciech Maziarz, Marek J. Los

DOI https://doi.org/10.7717/peerj.4125
Scientific Field Life & Health Sciences
Fellow Prof. Marek Los
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With the rapid advancement of regenerative medicine technologies, there is an urgent need for the development of new, cell-friendly techniques for obtaining nanofibers—the raw material for an artificial extracellular matrix production. We investigated the structure and properties of PCL10 nanofibers, PCL5/PCL10 core-shell type nanofibers, as well as PCL5/PCLAg nanofibres prepared by electrospinning. For the production of the fiber variants, a 5–10% solution of polycaprolactone (PCL) (Mw = 70,000–90,000), dissolved in a mixture of formic acid and acetic acid at a ratio of 70:30 m/m was used. In order to obtain fibers containing PCLAg 1% of silver nanoparticles was added. The electrospin was conducted using the above-described solutions at the electrostatic field. The subsequent bio-analysis shows that synthesis of core-shell nanofibers PCL5/PCL10, and the silver-doped variant nanofiber core shell PCL5/PCLAg, by using organic acids as solvents, is a robust technique. Furthermore, the incorporation of silver nanoparticles into PCL5/PCLAg makes such nanofibers toxic to model microbes without compromising its biocompatibility. Nanofibers obtained such way may then be used in regenerative medicine, for the preparation of extracellular scaffolds: (i) for controlled bone regeneration due to the long decay time of the PCL, (ii) as bioscaffolds for generation of other types of artificial tissues, (iii) and as carriers of nanocapsules for local drug delivery. Furthermore, the used solvents are significantly less toxic than the solvents for polycaprolactone currently commonly used in electrospin, like for example chloroform (CHCl3), methanol (CH3OH), dimethylformamide (C3H7NO) or tetrahydrofuran (C4H8O), hence the presented here electrospin technique may allow for the production of multilayer nanofibres more suitable for the use in medical field.