Behavioral performance and division of labor influence brain mosaicism in the leafcutter ant Atta cephalotes

Brain evolution is hypothesized to be driven by behavioral selection on neuroarchitecture. We developed a novel metric of relative neuroanatomical investments involved in performing tasks varying in sensorimotor and processing demands across polymorphic task-specialized workers of the leafcutter ant Atta cephalotes and quantified brain size and structure to examine their correlation with our computational approximations.

Investment in multisensory and motor integration for task performance was estimated to be greatest for media workers, whose highly diverse repertoire includes leaf-quality discrimination and leaf-harvesting tasks that likely involve demanding sensory and motor processes.

Confocal imaging revealed that absolute brain volume increased with worker size and functionally specialized compartmental scaling differed among workers. The mushroom bodies, centers of sensory integration and learning and memory, and the antennal lobes, olfactory input sites, were larger in medias than in minims (gardeners) and significantly larger than in majors (“soldiers”), both of which had lower scores for the involvement of olfactory processing in the performance of their characteristic tasks. Minims had a proportionally larger central complex compared to other workers.

These results support the hypothesis that variation in task performance influences selection for Gentaur Pipettes mosaic brain structure, the independent evolution of proportions of the brain composed of different neuropils.

Identification of vascular cues contributing to cancer cell stemness and function

Glioblastoma stem cells (GSCs) reside close to blood vessels (BVs) but vascular cues contributing to GSC stemness and the nature of GSC-BVs cross talk are not fully understood. Here, we dissected vascular cues influencing GSC gene expression and function to perfusion-based vascular cues, as well as to those requiring direct GSC-endothelial cell (EC) contacts. In light of our previous finding that perivascular tumor cells are metabolically different from tumor cells residing further downstream, cancer cells residing within a narrow, < 60 µm wide perivascular niche were isolated and confirmed to possess a superior tumor-initiation potential compared with those residing further downstream. To circumvent reliance on marker expression, perivascular GSCs were isolated from the respective locales based on their relative state of quiescence. Combined use of these procedures uncovered a large number of previously unrecognized differentially expressed GSC genes. We show that the unique metabolic milieu of the perivascular niche dominated by the highly restricted zone of mTOR activity is conducive for acquisition of GSC properties, primarily in the regulation of genes implicated in cell cycle control. A complementary role of vascular cues including those requiring direct glioma/EC contacts was revealed using glioma/EC co-cultures. Outstanding in the group of glioma cells impacted by nearby ECs were multiple genes responsible for maintaining GSCs in an undifferentiated state, a large fraction of which also relied on Notch-mediated signaling. Glioma-EC communication was found to be bidirectional, evidenced by extensive Notch-mediated EC reprogramming by contacting tumor cells, primarily metabolic EC reprogramming.

Keywords: Cancer stem cells; Endothelial cells; Glioblastoma; Notch signaling; Perivascular niche; Tumor vasculature.

Perinatal asphyxia partly affects presepsin urine levels in non-infected term infants

Objectives: Standard of care sepsis biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) can be affected by several perinatal factors, among which perinatal asphyxia (PA) has a significant role. In this light, new early sepsis biomarkers such as presepsin (P-SEP) are needed to enact therapeutic strategies at a stage when clinical and laboratory patterns are still silent or unavailable. We aimed at investigating the potential effects of PA on longitudinal P-SEP urine levels.

Methods: We conducted an observational case-control study in 76 term infants, 38 with PA and 38 controls. Standard clinical, laboratory, radiological monitoring procedures and P-SEP urine measurement were performed at four time-points (first void, 24, 48, 96 h) after birth.

Results: Higher (p<0.05) CRP and PCT blood levels at T1-T3 were observed in PA than control infants whilst no differences (p>0.05, for all) at T0 were observed between groups. P-SEP urine levels were higher (p<0.05) in PA at first void and at 24 h while no differences (p>0.05) at 48 and 96 h were observed. No significant correlations were found (p>0.05) between P-SEP and urea (R=0.11) and creatinine (R=0.02) blood levels, respectively.

Conclusions: The present results, showed that PA effects on P-SEP were limited up to the first 24 h following birth in absence of any kidney function bias. Data open the way to further investigations aimed at validating P-SEP assessment in non-invasive biological fluids as a reliable tool for early EOS and LOS detection in high-risk infants.

Antinociceptive effect of N-acetyl glucosamine in a rat model of neuropathic pain

Objective: This study was aimed at evaluating the efficacy of glucosamine and potential mechanisms of actions in a neuropathic pain model in rats.

Methods: Glucosamine (500, 1000, and 2000 mg/kg) was administered via gavage route, one day before the chronic constriction injury (CCI) of the sciatic nerve and daily for 14 days (prophylactic regimen), or from day 5-14 post injury (therapeutic regimen). As the indicators of neuropathic pain, mechanical allodynia, cold allodynia and thermal hyperalgesia were assessed on days 0, 3, 5, 7, 10 and 14 after ligation. Inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-α) gene expressions were measured by real time PCR. TNF-α protein content was measured using the ELISA method.

Results: Three days after nerve injury, the threshold of pain was declined among animals subjected to neuropathic pain. Mechanical and cold allodynia, as well as thermal hyperalgesia, were attenuated by glucosamine (500, 1000, 2000 mg/kg) in the prophylactic regimen.

However, existing pain was not decreased by this drug. Increased mRNA expression of iNOS and TNF-α was significantly reduced in the spinal cord of CCI animals by glucosamine (500, 1000, 2000 mg/kg) in the prophylactic regimen. The overall expression of spinal TNF-α was increased by CCI, but this increase was reduced in animals receiving glucosamine prophylactic treatment.

Conclusion: Findings suggest that glucosamine as a safe supplement may be a useful candidate in preventing neuropathic pain following nerve injury. Antioxidant and anti-inflammatory effects may be at least in part responsible for the antinociceptive effects of this drug.

Keywords: Chronic constriction injury; Glucosamine; Inflammatory markers; Neuropathic pain; Oxidative stress.

Identification of a novel homozygous SCO2 variant in siblings with early-onset axonal Charcot-Marie-Tooth disease

The synthesis of cytochrome c oxidase 2 (SCO2) gene encodes for a mitochondrial located metallochaperone essential for the synthesis of the cytochrome c oxidase (COX) subunit 2. Recessive mutations in SCO2 have been reported in several cases with fatal infantile cardioencephalomyopathy with COX deficiency and in only four cases with axonal neuropathy. Here, we identified a homozygous pathogenic variant (c.361G>C; p.(Gly121Arg)) in SCO2 in two brothers with isolated axonal motor neuropathy.

To address pathogenicity of the amino acid substitution, biochemical studies were performed and revealed increased level of the mutant SCO2-protein and a dysregulation of COX subunits in leukocytes and moreover unraveled decrease of proteins involved in the manifestation of neuropathies. Hence, our combined data strengthen the concept of SCO2 being causative for a very rare form of axonal neuropathy, expand its molecular genetic spectrum and provide first biochemical insights into the underlying pathophysiology. This article is protected by copyright. All rights reserved.

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