Suppression of adult cytogenesis in the rat brain leads to sex‐differentiated disruption of the HPA axis activity

ObjectivesThe action of stress hormones, mainly glucocorticoids, starts and coordinates the systemic response to stressful events. The HPA axis activity is predicated on information processing and modulation by upstream centres, such as the hippocampus where adult‐born neurons (hABN) have been reported to be an important component in the processing and integration of new information. Still, it remains unclear whether and how hABN regulates HPA axis activity and CORT production, particularly when considering sex differences.Materials and MethodsUsing both sexes of a transgenic rat model of cytogenesis ablation (GFAP‐Tk rat model), we examined the endocrinological and behavioural effects of disrupting the generation of new astrocytes and neurons within the hippocampal dentate gyrus (DG).ResultsOur results show that GFAP‐Tk male rats present a heightened acute stress response. In contrast, GFAP‐Tk female rats have increased corticosterone secretion at nadir, a heightened, yet delayed, response to an acute stress stimulus, accompanied by neuronal hypertrophy in the basal lateral amygdala and increased expression of the glucocorticoid receptors in the ventral DG.ConclusionsOur results reveal that hABN regulation of the HPA axis response is sex‐differentiated.     

Genomic Signatures of Recent Adaptation in a Wild Bumblebee

Environmental changes threaten insect pollinators, creating risks for agriculture and ecosystem stability. Despite their importance, we know little about how wild insects respond to environmental pressures. To understand the genomic bases of adaptation in an ecologically important pollinator, we analyzed genomes of Bombus terrestris bumblebees collected across Great Britain. We reveal extensive genetic diversity within this population, and strong signatures of recent adaptation throughout the genome affecting key processes including neurobiology and wing development. We also discover unusual features of the genome, including a region containing 53 genes that lacks genetic diversity in many bee species, and a horizontal gene transfer from a Wolbachia bacteria. Overall, the genetic diversity we observe and how it is distributed throughout the genome and the population should support the resilience of this important pollinator species to ongoing and future selective pressures. Applying our approach to more species should help understand how they can differ in their adaptive potential, and to develop conservation strategies for those most at risk.     

Promoting lab culture to enhance academic resilience during crises

The COVID‐19 pandemic has heavily impacted academics’ professional and personal lives, forcing many research groups (labs) to shift from an academic system primarily based on in‐person work to an almost full‐time remote workforce during lockdowns. Labs are generally characterized by a strong lab culture that underpins all research and social activities of its members. Lab culture traditionally builds on the pillars of in‐person communication, knowledge sharing, and all social and professional activities that promote collaboration, team building, scientific productivity, and well‐being. Here, we use the experience of our research group facing the COVID‐19 pandemic to illustrate how proactively reinforcing lab culture and its positive outcomes have been essential to our lab when transitioning from an in‐person to a remote lab environment, and through its ongoing evolution toward a hybrid remote/in‐person model. We argue that the proactive promotion of lab culture in research groups can foster academic resilience during crises, helping research groups to maintain their capacity to conduct scientific activities while preserving a sustainable life/work balance and a healthy mental condition.     

Common BMI and diabetes-related genetic variants: A pilot study among indigenous people in the Brazilian Amazon

This study was carried out to investigate the frequency of genetic variants related to body mass index (BMI) and type 2 diabetes (T2D) and evaluating the potential impact of risk alleles on susceptibility to these disorders in six indigenous peoples from Brazilian Amazon region. The majority of Fst values for pairwise population comparisons among the indigenous groups are low or moderate. The indigenous people show high values of differentiation with Africans, Europeans and Southeast Asians and moderate values with East Asian and American populations, as expected. The allelic frequencies among indigenous indicate that the majority of associations observed with T2D in continental populations can be replicated in native Amazonians. The genetic risk scores calculated for T2D in indigenous are high and similar to those calculated for Americans and East Asians, while the estimates obtained for obesity are low, probably due to the low frequencies of the risk allele of the FTO gene found in our samples. ADRB3-rs4994 and ABCC8-rs1799854 genes showed a significant association with BMI and waist circumference, and the KCNJ11-rs5219 gene with hyperglycemia. These results emphasize the importance of knowing the genetic variability underlying complex genetic diseases in indigenous peoples and the search for particular or rare variants. Keywords: T2D, BMI, SNP, Amerindians, Brazilian     

Application of the response surface methodology for optimization of whey protein partitioning in PEG/phosphate aqueous two-phase system

In order to develop a new strategy for β-lactoglobulin (β-lg) removal from whey protein, partitioning of α-lactalbumin (α-la), β-lg and glycomacropeptide (Gmp) was studied using aqueous two phase systems (ATPS). A system composed of 13% (w/w) polyethylene glycol (PEG, average molar mass 2000 g/mol) and 13% (w/w) potassium phosphate was used at 25°C. A central composite rotatable design (CCRD) associated to the response surface methodology (RSM) was applied to investigate the effects of NaCl concentration and pH on the partition of these proteins. It was found that α-la and Gmp partitioned to the top phase rich in PEG, whereas β-lg partitioned to the bottom phase rich in salt. According to the RSM, optimal conditions for β-lg removal where found where pH was equal to 6.7 and salt concentration was 0.35 mol/L. Under these conditions, the partition coefficient K(α) was 0.48 and K(Gmp) was 0.92. On the other hand, the partition coefficient K(β) was only 0.01. In such conditions β-lg preferentially concentrates in the bottom phase, while the top phase exclusively contains the proteins α-la and Gmp. Fractionation of the proteins from fresh whey was performed in a three stage cross-flow extraction system. The extraction yield for β-lg in the bottom phase was 97.3%, while the yields for α-la and Gmp in the top phase were 81.1% and 97.8%, respectively.     

Frequent simian foamy virus infection in persons occupationally exposed to nonhuman primates

The recognition that AIDS originated as a zoonosis heightens public health concerns associated with human infection by simian retroviruses endemic in nonhuman primates (NHPs). These retroviruses include simian immunodeficiency virus (SIV), simian T-cell lymphotropic virus (STLV), simian type D retrovirus (SRV), and simian foamy virus (SFV). Although occasional infection with SIV, SRV, or SFV in persons occupationally exposed to NHPs has been reported, the characteristics and significance of these zoonotic infections are not fully defined. Surveillance for simian retroviruses at three research centers and two zoos identified no SIV, SRV, or STLV infection in 187 participants. However, 10 of 187 persons (5.3%) tested positive for SFV antibodies by Western blot (WB) analysis. Eight of the 10 were males, and 3 of the 10 worked at zoos. SFV integrase gene (int) and gag sequences were PCR amplified from the peripheral blood lymphocytes available from 9 of the 10 persons. Phylogenetic analysis showed SFV infection originating from chimpanzees (n = 8) and baboons (n = 1). SFV seropositivity for periods of 8 to 26 years (median, 22 years) was documented for six workers for whom archived serum samples were available, demonstrating long-standing SFV infection. All 10 persons reported general good health, and secondary transmission of SFV was not observed in three wives available for WB and PCR testing. Additional phylogenetic analysis of int and gag sequences provided the first direct evidence identifying the source chimpanzees of the SFV infection in two workers. This study documents more frequent infection with SFV than with other simian retroviruses in persons working with NHPs and provides important information on the natural history and species origin of these infections. Our data highlight the importance of studies to better define the public health implications of zoonotic SFV infections.     

Apoptosis in transgenic mice expressing the P301L mutated form of human tau

The rTg4510 mouse is a tauopathy model, characterized by massive neurodegeneration in Alzheimer's disease (AD)-relevant cortical and limbic structures, deficits in spatial reference memory, and progression of neurofibrillary tangles (NFT). In this study, we examined the role of apoptosis in neuronal loss and associated tau pathology. The results showed that DNA fragmentation and caspase-3 activation are common in the hippocampus and frontal cortex of young rTg4510 mice. These changes were associated with cleavage of tau into smaller intermediate fragments, which persist with age. Interestingly, active caspase-3 was often co-localized with cleaved tau. In vitro, fibrillar Abeta(1-42) resulted in nuclear fragmentation, caspase activation, and caspase-3-induced cleavage of tau. Notably, incubation with the antiapoptotic molecule tauroursodeoxycholic acid abrogated apoptosis-mediated cleavage of tau in rat cortical neurons. In conclusion, caspase-3-cleaved intermediate tau species occurred early in rTg54510 brains and preceded cell loss in Abeta-exposed cultured neurons. These results suggest a potential role of apoptosis in neurodegeneration.     

Antibiotic‐Potentiating Activity of Phanostenine Isolated from Cissampelos sympodialis Eichler

Cissampelos sympodialis Eichler is well studied and investigated for its antiasthmatic properties, but there are no data in the literature describing antibacterial properties of alkaloids isolated from this botanical species. This work reports the isolation and characterization of phanostenine obtained from roots of C. sympodialis and describes for the first time its antimicrobial and antibiotic modulatory properties. Phanostenine was first isolated from Cissampelos sympodialis and its antibacterial activities were determined. Chemical structures of the alkaloid isolate were determined using spectroscopic and chemical analyses. Phanostenine was also tested for its antibacterial activity against standard strains and clinical isolates of Escherichia coli and Staphylococcus aureus. Minimal inhibitory concentration (MIC) was determined in a microdilution assay and for the evaluation of antibiotic resistance‐modifying activity. MIC of the antibiotics was determined in the presence or absence of phanostenine at sub‐inhibitory concentrations. The evaluation of antibacterial activity by microdilution assay showed activity for all strains with better values against S. aureus ATCC 12692 and E. coli 27 (787.69 mm ). The evaluation of aminoglycoside antibiotic resistance‐modifying activity showed reduction in the MIC of the aminoglycosides (amikacin, gentamicin and neomycin) when associated with phanostenine, MIC reduction of antibiotics ranging from 21 % to 80 %. The data demonstrated that phanostenine possesses a relevant ability to modify the antibiotic activity in vitro. We can suggest that phanostenine presents itself as a promising tool as an adjuvant for novel antibiotics formulations against bacterial resistance.