Expansion of Pathogen-Specific Mono- and Multifunctional Th1 and Th17 Cells in Multi-Focal Tuberculous Lymphadenitis

Background

Th1 and Th17 responses are known to play an important role in immunity to pulmonary tuberculosis (PTB), although little is known about their role in extrapulmonary forms of tuberculosis (TB).

Methods

To identify the role of Th1, Th17, and Th22 cells in multi-focal TB lymphadenitis (TBL), we examined mycobacteria–specific immune responses in the whole blood of individuals with PTB (n = 20) and compared them with those with TBL (n = 25).

Results

Elevated frequencies of CD4⁺ T cells expressing IFN- γ, TNF-α, and IL-2 were present in individuals with TBL compared with those with PTB at baseline and in response to ESAT-6 and CFP-10. Similarly, increased frequencies of CD4⁺ T cells expressing IL-17A, IL-17F, and IFN-γ were also present in individuals with TBL at baseline and following ESAT-6 and CFP-10 stimulation although no significant difference in frequency of Th22 cells was observed. Finally, frequencies of Th1 (but not Th17) cells exhibited a significantly negative correlation with natural regulatory T cell frequencies at baseline.

Conclusions

Multi-focal TB lymphadenitis is therefore characterized by elevated frequencies of Th1 and Th17 cells, indicating that Th1 and Th17 responses in TB disease are probably correlates of disease severity rather than of protective immunity.     

Triglyceride/HDL Ratio as a Screening Tool for Predicting Success at Reducing Anti-Diabetic Medications Following Weight Loss

Background and Objectives

Intentional weight loss, by reducing insulin resistance, results in both better glycemic control and decreased need for anti-diabetic medications. However, not everyone who is successful with weight loss is able to reduce anti-diabetic medication use. In this retrospective cohort study, we assessed the predictive accuracy of baseline triglyceride (TGL)/HDL ratio, a marker of insulin resistance, to screen patients for success in reducing anti-diabetic medication use with weight loss.

Methods

Case records of 121 overweight and obese attendees at two outpatient weight management centers were analyzed. The weight loss intervention consisted of a calorie-restricted diet (~1000Kcal/day deficit), a behavior modification plan, and a plan for increasing physical activity.

Results

Mean period of follow-up was 12.5 ± 3.5 months. By study exit, mean weight loss and mean HbA1c% reduction were 15.4 ± 5.5 kgs and 0.5 ± 0.2% respectively. 81 (67%) in the study cohort achieved at least 1 dose reduction of any anti-diabetic medication. Tests for predictive accuracy of baseline TGL/HDL ratio ≤ 3 to determine success with dose reductions of anti-diabetic medications showed a sensitivity, specificity, positive predictive value, negative predictive value, area under the curve, likelihood ratio (LR) + and LR-of 81, 83, 90, 70, 78, 4.8 and 0.2, respectively. Reproducibility of TGL/HDL ratio was acceptable.

Conclusion

TGL/HDL ratio shows promise as an effective screening tool to determine success with dose reductions of anti-diabetic medications. The results of our study may inform the conduct of a systematic review using data from prior weight loss trials.     

Modelling Adaptation to Directional Motion Using the Adelson-Bergen Energy Sensor

The motion energy sensor has been shown to account for a wide range of physiological and psychophysical results in motion detection and discrimination studies. It has become established as the standard computational model for retinal movement sensing in the human visual system. Adaptation effects have been extensively studied in the psychophysical literature on motion perception, and play a crucial role in theoretical debates, but the current implementation of the energy sensor does not provide directly for modelling adaptation-induced changes in output. We describe an extension of the model to incorporate changes in output due to adaptation. The extended model first computes a space-time representation of the output to a given stimulus, and then a RC gain-control circuit (“leaky integrator”) is applied to the time-dependent output. The output of the extended model shows effects which mirror those observed in psychophysical studies of motion adaptation: a decline in sensor output during stimulation, and changes in the relative of outputs of different sensors following this adaptation.     

Propyl-2-(8-(3,4-Difluorobenzyl)-2′,5′-Dioxo-8-Azaspiro[Bicyclo[3.2.1] Octane-3,4′-Imidazolidine]-1′-yl) Acetate Induces Apoptosis in Human Leukemia Cells through Mitochondrial Pathway following Cell Cycle Arrest

Background

Due to the functional defects in apoptosis signaling molecules or deficient activation of apoptosis pathways, leukemia has become an aggressive disease with poor prognosis. Although the majority of leukemia patients initially respond to chemotherapy, relapse is still the leading cause of death. Hence targeting apoptosis pathway would be a promising strategy for the improved treatment of leukemia. Hydantoin derivatives possess a wide range of important biological and pharmacological properties including anticancer properties. Here we investigated the antileukemic activity and mechanism of action of one of the potent azaspiro hydantoin derivative, (ASHD).

Materials and Methods

To investigate the antileukemic efficacy of ASHD, we have used MTT assay, cell cycle analysis by FACS, tritiated thymidine incorporation assay, Annexin V staining, JC1 staining and western blot analysis.

Results

Results showed that ASHD was approximately 3-fold more potent than the parent compounds in inducing cytotoxicity. Tritiated thymidine assay in conjunction with cell cycle analysis suggests that ASHD inhibited the growth of leukemic cells. The limited effect of ASHD on cell viability of normal cells indicated that it may be specifically directed to cancer cells. Translocation of phosphatidyl serine, activation of caspase 3, caspase 9, PARP, alteration in the ratio of BCL2/BAD protein expression as well as the loss of mitochondrial membrane potential suggests activation of the intrinsic pathway of apoptosis.

Conclusion

These results could facilitate the future development of novel hydantoin derivatives as chemotherapeutic agents for leukemia.     

At least two indigenous species of the Bemisia tabaci complex are present in Brazil

Bemisia tabaci is one of the most important global agricultural insect pests, being a vector of emerging plant viruses such as begomoviruses and criniviruses that cause serious problems in many countries. Although knowledge of the genetic diversity of B. tabaci populations is important for controlling this pest and understanding viral epidemics, limited information is available on this pest in Brazil. A survey was conducted in different locations of São Paulo and Mato Grosso states, and the phylogenetic relationships of B. tabaci individuals from 43 populations sampled from different hosts were analysed based on partial mitochondrial cytochrome oxidase 1 gene (mtCOI) sequences. According to the recently proposed classification of the B. tabaci complex, which employs the 3.5% mtCOI sequence divergence threshold for species demarcation, most of the specimens collected were found to belong to the Middle East‐Asia Minor 1 species, which includes the invasive populations of the commonly known B biotype, within the Africa/Middle East/Asia Minor high‐level group. Three specimens collected from Solanun gilo and Ipomoea sp. were grouped together and could be classified in the New World species that includes the commonly known A biotype. However, six specimens collected from Euphorbia heterophylla, Xanthium cavanillesii and Glycine maxima could not be classified into any of the 28 previously proposed species, although according to the 11% mtCOI sequence divergence threshold, they belong to the New World high‐level group. These specimens were classified into a new recently proposed species named New World 2 that includes populations from Argentina. Middle East‐Asia Minor 1, New World and New World 2 were differentiated by RFLP analysis of the mtCOI gene using TaqI enzyme. Taq I analysis in silico also differentiates these from Mediterranean species, thus making this method a convenient tool to determine population dynamics, especially critical for monitoring the presence of this exotic pest in Brazil.     

Is the existence of a mutualistic relationship between Lobesia botrana and Botrytis cinerea well-founded?

Some studies have highlighted benefits for Lobesia botrana by adding Botrytis cinerea mycelium to an artificial larval diet and have suggested a mutualistic relationship between the two organisms on grapevine, hypothesizing that fungal sterols were the nutritional factor involved. Because the nutritional quality of an artificial diet should be similar to grapes to allow extrapolation of the results to the field conditions, in the current study L. botrana larval performance was compared when larvae were fed on grapes (berries) or two artificial diets either with or without enrichment with B. cinerea. Based on sterol analysis, the two artificial diets had high cholesterol content, but relative to berries showed comparable and low phytosterol contents, respectively (high- and low-phytosterol, HPh, and LPh). While larval fitness on the HPh diet was similar to berries, the LPh diet led to higher mortality and worse larval performance. The addition of the fungus compensated for the shortage in the LPh diet but did not improve the HPh diet. Supplementing the LPh diet with linoleic acid, which is supplied also from B. cinerea, partially improved larval performance. In a field experiment, females did not show any egg-laying preferences towards naturally botrytized bunches. The positive effect of B. cinerea on the moth's next generation that is reported in the literature could be a consequence of fungus developed inside berry tunnels bored by larvae. Therefore, based on our data and previous reports the existence of a mutualistic relationship between L. botrana and B. cinerea is not well-founded.     

Chromosomal markers in Parodontidae: an analysis of new and reviewed data with phylogenetic inferences

The taxonomy of the family Parodontidae is confused, with many open questions regarding the most appropriate generic groupings. Studies on the organization, structure, composition, and in situ location of chromosomal features have led to consistent advances in the understanding of genome evolution. Among the species of Parodontidae, the consistent chromosomal divergences can be helpful in taxonomic classification, such as heteromorphic chromosome sex, karyotypic formulae, and number/location of the repetitive DNAs. Molecular analysis of repetitive sequences of satellite DNA and their physical mapping in the chromosomes of different species in a single group may be used to infer evolutionary divergence and cladistic grouping. In the present study, rDNA and the satellite DNA pPh2004 were mapped by fluorescent in situ hybridization on the chromosomes of some species of Parodontidae. These results were analyzed and reviewed together with other chromosomal markers and previously published data, to formulate inferences about the diversification of the genomes and propose a clustering of some Parodontidae species. This analysis indicated that the species Apareiodon affinis, Parodon moreirai, Parodon hilarii, Parodon nasus, and Parodon pongoensis have an apomorphic state for satellite DNA pPh2004 in Parodontidae in relation to previously studied species of Apareiodon.     

From the Wuhan-Hu-1 strain to the XD and XE variants: is targeting the SARS-CoV-2 spike protein still a pharmaceutically relevant option against COVID-19?

Since the outbreak of the COVID-19 pandemic in December 2019, the SARS-CoV-2 genome has undergone several mutations. The emergence of such variants has resulted in multiple pandemic waves, contributing to sustaining to date the number of infections, hospitalisations, and deaths despite the swift development of vaccines, since most of these mutations are concentrated on the Spike protein, a viral surface glycoprotein that is the main target for most vaccines. A milestone in the fight against the COVID-19 pandemic has been represented by the development of Paxlovid, the first orally available drug against COVID-19, which acts on the Main Protease (Mpro). In this article, we analyse the structural features of both the Spike protein and the Mpro of the recently reported SARS-CoV-2 variant XE, as well the closely related XD and XF ones, discussing their impact on the efficacy of existing treatments against COVID-19 and on the development of future ones.     

Cytogenetic analysis of three sympatric Gymnotus (Gymnotiformes, Gymnotidae) species verifies invasive species in the Upper Paraná River basin, Brazil

Cytogenetic analyses were performed on three Gymnotus species, Gymnotus paraguensis , Gymnotus sylvius and Gymnotus pantanal , collected in sympatry in the region of Guaíra, Paraná State (Brazil). Gymnotus paraguensis presented 54 chromosomes (52m-sm + 2st) in both sexes, G. sylvius presented 40 chromosomes (36m-sm + 4a) in both sexes and G. pantanal presented 40 chromosomes (14m-sm + 26a) in females and 39 (15m-sm + 24a) in males, with an X₁X₁X₂X₂/X₁X₂Y multiple sex chromosome system. All three species had single nucleolar organizing regions and heterochromatin in the centromeric region of most chromosomes. Gymnotus pantanal , previously collected only in the Lower Paraná and Paraguay River basins, was confirmed for the first time in the Upper Paraná River basin. This species constitutes one of several examples of species that have colonized the region after flooding of the great Sete Quedas waterfalls by the construction of the Itaipu hydroelectric dam. The probable absence or infertility of hybrids is indicated by the high level of chromosome differentiation between these species.