Integrative analysis in toxicological assessment of the insecticide Malathion in Allium cepa L. system

For many centuries human populations have been suffering and trying to fight with disease-bearing mosquitoes. Emerging and reemerging diseases such as Dengue, Zika, and Chikungunya affect billions of people around the world and recently has been appealing to control with chemical pesticides. Malathion (MT) is one of the main pesticides used against mosquitoes, the vectors of these diseases. This study aimed to assess cytotoxicity and mutagenicity of the malathion for the bioindicator Allium cepa L. using a multivariate and integrative approach. Moreover, an appendix table was compiled with all available literature of insecticides assessed by the Allium cepa system to support our discussion. Exposures during 48h to 0.5 mg mL-1 and 1.0 mg mL-1 MT were compared to the negative control (distilled water) and positive control (MMS solution at 10 mg L-1). The presence of chromosomal aberrations, micronuclei frequency, and mitotic index abnormalities was evaluated. Anaphase bridges were the alterations with higher incidence and presented a significantly elevated rate in the concentration of 0.5 mg mL-1, including when compared to the positive control. The integrative discriminant analysis summarizes that MT in assessed concentrations presented effects like the positive control, corroborating its potential of toxicity to DNA. Therefore, it is concluded that MT in its pure composition and in realistic concentrations used, has genotoxic potential in the biological assessment of A. cepa cells. The multivariate integrative analysis was fundamental to show a whole response of all data, providing a global view of the effect of MT on DNA.

Genome-Wide Analysis in Drosophila Reveals the Genetic Basis of Variation in Age-Specific Physical Performance and Response to ACE Inhibition

Despite impressive results in restoring physical performance in rodent models, treatment with renin–angiotensin system (RAS) inhibitors, such as Lisinopril, have highly mixed results in humans, likely, in part, due to genetic variation in human populations. To date, the genetic determinants of responses to drugs, such as RAS inhibitors, remain unknown. Given the complexity of the relationship between physical traits and genetic background, genomic studies which predict genotype- and age-specific responses to drug treatments in humans or vertebrate animals are difficult. Here, using 126 genetically distinct lines of Drosophila melanogaster, we tested the effects of Lisinopril on age-specific climbing speed and endurance. Our data show that functional response and sensitivity to Lisinopril treatment ranges from significant protection against physical decline to increased weakness depending on genotype and age. Furthermore, genome-wide analyses led to identification of evolutionarily conserved genes in the WNT signaling pathway as being significantly associated with variations in physical performance traits and sensitivity to Lisinopril treatment. Genetic knockdown of genes in the WNT signaling pathway, Axin, frizzled, nemo, and wingless, diminished or abolished the effects of Lisinopril treatment on climbing speed traits. Our results implicate these genes as contributors to the genotype- and age-specific effects of Lisinopril treatment and because they have orthologs in humans, they are potential therapeutic targets for improvement of resiliency. Our approach should be widely applicable for identifying genomic variants that predict age- and sex-dependent responses to any type of pharmaceutical treatment.

Are there non-linear relationships between alcohol consumption and long-term health?: a systematic review of observational studies employing approaches to improve causal inference

Background Research has long found ‘J-shaped’ relationships between alcohol consumption and certain health outcomes, indicating a protective effect of moderate consumption. However, methodological limitations in most studies hinder causal inference. This review aimed to identify all observational studies employing improved approaches to mitigate confounding in characterizing alcohol–long-term health relationships, and to qualitatively synthesize their findings. Methods Eligible studies met the above description, were longitudinal (with pre-defined exceptions), discretized alcohol consumption, and were conducted with human populations. MEDLINE, PsycINFO, Embase and SCOPUS were searched in May 2020, yielding 16 published manuscripts reporting on cancer, diabetes, dementia, mental health, cardiovascular health, mortality, HIV seroconversion, and musculoskeletal health. Risk of bias of cohort studies was evaluated using the Newcastle-Ottawa Scale, and a recently developed tool was used for Mendelian Randomization studies. Results A variety of functional forms were found, including reverse J/J-shaped relationships for prostate cancer and related mortality, dementia risk, mental health, and certain lipids. However, most outcomes were only evaluated by a single study, and few studies provided information on the role of alcohol consumption pattern. Conclusions More research employing enhanced causal inference methods is urgently required to accurately characterize alcohol–long-term health relationships. Those studies that have been conducted find a variety of linear and non-linear functional forms, with results tending to be discrepant even within specific health outcomes. Trial registration PROSPERO registration number CRD42020185861.

Trait-Based Vaccination of Individual Meerkats (Suricata suricatta) against Tuberculosis Provides Evidence to Support Targeted Disease Control

Individuals vary in their potential to acquire and transmit infections, but this fact is currently underexploited in disease control strategies. We trialled a trait-based vaccination strategy to reduce tuberculosis in free-living meerkats by targeting high-contact meerkats (socially dominant individuals) in one study arm, and high-susceptibility individuals (young subordinates) in a second arm. We monitored infection within vaccinated groups over two years comparing the results with untreated control groups. Being a member of a high-contact group had a protective effect on individuals’ survival times (Hazard Ratio = 0.5, 95% Confidence Interval, CI: 0.29–0.88, p = 0.02) compared to control groups. Over the study, odds of testing positive for tuberculosis increased more than five-fold in control groups (Odds Ratio = 5.40, 95% CI = 0.94–30.98, p = 0.058); however, no increases were observed in either of the treatment arms. Targeted disease control approaches, such as the one described in this study, allow for reduced numbers of interventions. Here, trait-based vaccination was associated with reduced infection rates and thus has the potential to offer more efficient alternatives to traditional mass-vaccination policies. Such improvements in efficiency warrant further study and could make infectious disease control more practically achievable in both animal (particularly wildlife) and human populations.

Simultaneous Dissection of Grain Carotenoid Levels and Kernel Color in Biparental Maize Populations with Yellow-to-Orange Grain

ABSTRACT Maize enriched in provitamin A carotenoids could be key in combatting vitamin A deficiency in human populations relying on maize as a food staple. Consumer studies indicate that orange maize may be regarded as novel and preferred. This study identifies genes of relevance for grain carotenoid concentrations and kernel color, through simultaneous dissection of these traits in 10 families of the U.S. maize nested association mapping panel that have yellow to orange grain. Quantitative trait loci (QTL) were identified via joint-linkage analysis, with phenotypic variation explained for individual kernel color QTL ranging from 2.4 to 17.5%. These QTL were cross-analyzed with significant marker-trait associations in a genome-wide association study that utilized ∼27 million variants. Nine genes were identified: four encoding activities upstream of the core carotenoid pathway, one at the pathway branchpoint, three within the α- or β-pathway branches, and one encoding a carotenoid cleavage dioxygenase. Of these, three exhibited significant pleiotropy between kernel color and one or more carotenoid traits. Kernel color exhibited moderate positive correlations with β-branch and total carotenoids and negligible correlations with α-branch carotenoids. These findings can be leveraged to simultaneously achieve desirable kernel color phenotypes and increase concentrations of provitamin A and other priority carotenoids.

Experimental Susceptibility of North American Raccoons (Procyon lotor) and Striped Skunks (Mephitis mephitis) to SARS-CoV-2

Recent spillback events of SARS-CoV-2 from humans to animals has raised concerns about it becoming endemic in wildlife. A sylvatic cycle of SARS-CoV-2 could present multiple opportunities for repeated spillback into human populations and other susceptible wildlife. Based on their taxonomy and natural history, two native North American wildlife species —the striped skunk (Mephitis mephitis) and the raccoon (Procyon lotor) —represent a high likelihood of susceptibility and ecological opportunity of becoming infected with SARS-CoV-2. Eight skunks and raccoons were each intranasally inoculated with one of two doses of the virus (103 PFU and 105 PFU) and housed in pairs. To evaluate direct transmission, a naïve animal was added to each inoculated pair 48 h post-inoculation. Four control animals of each species were handled like the experimental groups. At predetermined intervals, we collected nasal and rectal swabs to quantify virus shed via virus isolation and detect viral RNA via rRT-PCR and blood for serum neutralization. Lastly, animals were euthanized at staggered intervals to describe disease progression through histopathology and immunohistochemistry. No animals developed clinical disease. All intranasally inoculated animals seroconverted, suggesting both species are susceptible to SARS-CoV-2 infection. The highest titers in skunks and raccoons were 1:128 and 1:64, respectively. Low quantities of virus were isolated from 2/8 inoculated skunks for up to day 5 post-inoculation, however no virus was isolated from inoculated raccoons or direct contacts of either species. Neither species had gross lesions, but recovering mild chronic pneumonia consistent with viral insult was recorded histologically in 5/8 inoculated skunks. Unlike another SARS-CoV-2 infection trial in these species, we detected neutralizing antibodies in inoculated raccoons; thus, future wildlife serologic surveillance results must be interpreted with caution. Due to the inability to isolate virus from raccoons, the lack of evidence of direct transmission between both species, and low amount of virus shed by skunks, it seems unlikely for SARS-CoV-2 to become established in raccoon and skunk populations and for virus to spillback into humans. Continued outbreaks in non-domestic species, wild and captive, highlight that additional research on the susceptibility of SARS-CoV-2 in wildlife, especially musteloidea, and of conservation concern, is needed.

An M protein coiled coil unfurls and exposes its hydrophobic core to capture LL-37

Surface-associated, coiled-coil M proteins of Streptococcus pyogenes (Strep A) disable human immunity through interaction with select proteins. However, coiled coils lack features typical of protein-protein interaction sites, and it is therefore challenging to understand how M proteins achieve specific binding, for example, with the human antimicrobial peptide LL-37, which results in its neutralization. The crystal structure of a complex of LL-37 with M87 protein, an antigenic variant from a strain that is an emerging threat, revealed a novel interaction mode. The M87 coiled coil unfurled and asymmetrically exposed its hydrophobic core to capture LL-37. A single LL-37 molecule bound M87 in the crystal, but in solution recruited additional LL-37 molecules, consistent with a protein trap neutralization mechanism. The interaction mode visualized crystallographically was verified to contribute significantly to LL-37 resistance in an M87 Strep A strain, and was identified to be conserved in a number of other M protein types that are prevalent in human populations. Our results provide specific detail for therapeutic inhibition of LL-37 neutralization by M proteins.

Rethinking the Role of Nitrogen and Phosphorus in the Eutrophication of Aquatic Ecosystems

Nitrogen and phosphorus are two nutrients that are essential for the growth and survival of plants and animals but are often present in short supply. Both nitrogen and phosphorus are applied regularly through fertilizer to increase the yield of crops needed to feed human populations and for residential and commercial landscaping purposes. This publication contains information for stakeholders, students, scientists, and environmental agencies interested in understanding how nitrogen and phosphorus affect water resources. Major revision by Ashley Smyth, H. Dail Laughinghouse IV, Karl Havens, and Thomas Frazer; 5 pp.https://edis.ifas.ufl.edu/sg118

Cancer-driving mutations are enriched in genic regions intolerant to germline variation

Large reference datasets of protein-coding variation in human populations have allowed us to determine which genes and genic sub-regions are intolerant to germline genetic variation. There is also a growing number of genes implicated in severe Mendelian diseases that overlap with genes implicated in cancer. Here, we hypothesized that mitotically mutable genic sub-regions that are intolerant to germline variation are enriched for cancer-driving mutations. We introduce a new metric, OncMTR, which uses 125,748 exomes in the gnomAD database to identify genic sub-regions intolerant to germline variation but enriched for hematologic somatic variants. We demonstrate that OncMTR can significantly predict driver mutations implicated in hematologic malignancies. Divergent OncMTR regions were enriched for cancer-relevant protein domains, and overlaying OncMTR scores on protein structures identified functionally important protein residues. Finally, we performed a rare variant, gene-based collapsing analysis on an independent set of 394,694 exomes from the UK Biobank and find that OncMTR dramatically improves genetic signals for hematologic malignancies. Our web app enables easy visualization of OncMTR scores for each protein-coding gene (https://astrazeneca-cgr-publications.github.io/OncMTR-Viewer/).

Facial and body sexual dimorphism are not interconnected in the Maasai

Background In this paper, we investigate facial sexual dimorphism and its’ association with body dimorphism in Maasai, the traditional seminomadic population of Tanzania. We discuss findings on other human populations and possible factors affecting the developmental processes in Maasai. Methods Full-face anthropological photographs were obtained from 305 Maasai (185 men, 120 women) aged 17–90 years. Facial shape was assessed combining geometric morphometrics and classical facial indices. Body parameters were measured directly using precise anthropological instruments. Results Sexual dimorphism in Maasai faces was low, sex explained 1.8% of the total shape variance. However, male faces were relatively narrower and vertically prolonged, with slightly wider noses, narrower-set and lower eyebrows, wider mouths, and higher forehead hairline. The most sexually dimorphic regions of the face were the lower jaw and the nose. Facial width-to-height ratio (fWHR), measured in six known variants, revealed no significant sexual dimorphism. The allometric effects on facial traits were mostly related to the face growth, rather than the growth of the whole body (body height). Significant body dimorphism was demonstrated, men being significantly higher, with larger wrist diameter and hand grip strength, and women having higher BMI, hips circumferences, upper arm circumferences, triceps skinfolds. Facial and body sexual dimorphisms were not associated. Conclusions Facial sex differences in Maasai are very low, while on the contrary, the body sexual dimorphism is high. There were practically no associations between facial and body measures. These findings are interpreted in the light of trade-offs between environmental, cultural, and sexual selection pressures.