Introduced Drosophila subobscura populations perform better than native populations during an oviposition choice task due to increased fecundity but similar learning ability

The success of invasive species is tightly linked to their fitness in a putatively novel environment. While quantitative components of fitness have been studied extensively in the context of invasive species, fewer studies have looked at qualitative components of fitness, such as behavioral plasticity, and their interaction with quantitative components, despite intuitive benefits over the course of an invasion. In particular, learning is a form of behavioral plasticity that makes it possible to finely tune behavior according to environmental conditions. Learning can be crucial for survival and reproduction of introduced organisms in novel areas, for example, for detecting new predators, or finding mates or oviposition sites. Here we explored how oviposition performance evolved in relation to both fecundity and learning during an invasion, using native and introduced Drosophila subobscura populations performing an ecologically relevant task. Our results indicated that, under comparable conditions, invasive populations performed better during our oviposition task than did native populations. This was because invasive populations had higher fecundity, together with similar cognitive performance when compared to native populations, and that there was no interaction between learning and fecundity. Unexpectedly, our study did not reveal an allocation trade‐off (i.e., a negative relationship) between learning and fecundity. On the contrary, the pattern we observed was more consistent with an acquisition trade‐off, meaning that fecundity could be limited by availability of resources, unlike cognitive ability. This pattern might be the consequence of escaping natural enemies and/or competitors during the introduction. The apparent lack of evolution of learning may indicate that the introduced population did not face novel cognitive challenges in the new environment (i.e., cognitive “pre‐adaptation”). Alternatively, the evolution of learning may have been transient and therefore not detected.     

Oral Implant-Prostheses: New Teeth for a Brighter Brain

Several studies have demonstrated that chewing can be regarded as a preventive measure for cognitive impairment, whereas masticatory deficiency, associated with soft-diet feeding, is a risk factor for the development of dementia. At present the link between orofacial sensorimotor activity and cognitive functions is unknown. In subjects with unilateral molar loss we have shown asymmetries in both pupil size and masticatory muscles electromyographic (EMG) activity during clenching: the molar less side was characterized by a lower EMG activity and a smaller pupil. Since implant-prostheses, greatly reduced both the asymmetry in EMG activity and in pupil’s size, trigeminal unbalance, leading to unbalance in the activity of the Locus Coeruleus (LC), may be responsible for the pupil’s asymmetry. According to the findings obtained in animal models, we propose that the different activity of the right and left LC may induce an asymmetry in brain activity, thus leading to cognitive impairment. According to this hypothesis, prostheses improved the performance in a complex sensorimotor task and increased the mydriasis associated with haptic tasks. In conclusion, the present study indicates that the implant-prosthesis therapy, which reduces the unbalance of trigeminal proprioceptive afferents and the asymmetry in pupil’s size, may improve arousal, boosting performance in a complex sensorimotor task.     

Barcoding Eophila crodabepis sp. nov. (Annelida,Oligochaeta, Lumbricidae), a Large Stripy Earthworm from Alpine Foothills of Northeastern Italy Similar to Eophila tellinii (Rosa, 1888)

A new Italian earthworm morphologically close to the similarly large and anecic Eophila tellinii (Rosa, 1888) is described. Distribution of Eophila crodabepis sp. nov. extends over 750 km² from East to West on the Asiago Plateau and Vittorio Veneto Hills, from North to South on mounts Belluno Prealps (Praderadego and Cesen), Asiago, Grappa and onto the Montello foothills. This range abuts that of Eophila tellinii in northern Friuli Venezia Giulia region. Known localities of both E. tellinii and E.crodabepis sp. nov. are mapped. mtDNA barcoding definitively separates the new western species from classical Eophila tellinii (Rosa, 1888).     

Motor Adaptations to Pain during a Bilateral Plantarflexion Task: Does the Cost of Using the Non-Painful Limb Matter?

During a force-matched bilateral task, when pain is induced in one limb, a shift of load to the non-painful leg is classically observed. This study aimed to test the hypothesis that this adaptation to pain depends on the mechanical efficiency of the non-painful leg. We studied a bilateral plantarflexion task that allowed flexibility in the relative force produced with each leg, but constrained the sum of forces from both legs to match a target. We manipulated the mechanical efficiency of the non-painful leg by imposing scaling factors: 1, 0.75, or 0.25 to decrease mechanical efficiency (Decreased efficiency experiment: 18 participants); and 1, 1.33 or 4 to increase mechanical efficiency (Increased efficiency experiment: 17 participants). Participants performed multiple sets of three submaximal bilateral isometric plantarflexions with each scaling factor during two conditions (Baseline and Pain). Pain was induced by injection of hypertonic saline into the soleus. Force was equally distributed between legs during the Baseline contractions (laterality index was close to 1; Decreased efficiency experiment: 1.16±0.33; Increased efficiency experiment: 1.11±0.32), with no significant effect of Scaling factor. The laterality index was affected by Pain such that the painful leg contributed less than the non-painful leg to the total force (Decreased efficiency experiment: 0.90±0.41, P<0.001; Increased efficiency experiment: 0.75±0.32, P<0.001), regardless of the efficiency (scaling factor) of the non-painful leg. When compared to the force produced during Baseline of the corresponding scaling condition, a decrease in force produced by the painful leg was observed for all conditions, except for scaling 0.25. This decrease in force was correlated with a decrease in drive to the soleus muscle. These data highlight that regardless of the overall mechanical cost, the nervous system appears to prefer to alter force sharing between limbs such that force produced by the painful leg is reduced relative to the non-painful leg.     

Summed Probability Distribution of 14C Dates Suggests Regional Divergences in the Population Dynamics of the Jomon Period in Eastern Japan

Recent advances in the use of summed probability distribution (SPD) of calibrated ¹⁴C dates have opened new possibilities for studying prehistoric demography. The degree of correlation between climate change and population dynamics can now be accurately quantified, and divergences in the demographic history of distinct geographic areas can be statistically assessed. Here we contribute to this research agenda by reconstructing the prehistoric population change of Jomon hunter-gatherers between 7,000 and 3,000 cal BP. We collected 1,433 ¹⁴C dates from three different regions in Eastern Japan (Kanto, Aomori and Hokkaido) and established that the observed fluctuations in the SPDs were statistically significant. We also introduced a new non-parametric permutation test for comparing multiple sets of SPDs that highlights point of divergences in the population history of different geographic regions. Our analyses indicate a general rise-and-fall pattern shared by the three regions but also some key regional differences during the 6^th millennium cal BP. The results confirm some of the patterns suggested by previous archaeological studies based on house and site counts but offer statistical significance and an absolute chronological framework that will enable future studies aiming to establish potential correlation with climatic changes.     

Shape-Related Toxicity of Titanium Dioxide Nanofibres

Titanium dioxide (TiO₂) nanofibres are a novel fibrous nanomaterial with increasing applications in a variety of fields. While the biological effects of TiO₂ nanoparticles have been extensively studied, the toxicological characterization of TiO₂ nanofibres is far from being complete. In this study, we evaluated the toxicity of commercially available anatase TiO₂ nanofibres using TiO₂ nanoparticles (NP) and crocidolite asbestos as non-fibrous or fibrous benchmark materials. The evaluated endpoints were cell viability, haemolysis, macrophage activation, trans-epithelial electrical resistance (an indicator of the epithelial barrier competence), ROS production and oxidative stress as well as the morphology of exposed cells. The results showed that TiO₂ nanofibres caused a cell-specific, dose-dependent decrease of cell viability, with larger effects on alveolar epithelial cells than on macrophages. The observed effects were comparable to those of crocidolite, while TiO₂ NP did not decrease cell viability. TiO₂ nanofibres were also found endowed with a marked haemolytic activity, at levels significantly higher than those observed with TiO₂ nanoparticles or crocidolite. Moreover, TiO₂ nanofibres and crocidolite, but not TiO₂ nanoparticles, caused a significant decrease of the trans-epithelial electrical resistance of airway cell monolayers. SEM images demonstrated that the interaction with nanofibres and crocidolite caused cell shape perturbation with the longest fibres incompletely or not phagocytosed. The expression of several pro-inflammatory markers, such as NO production and the induction of Nos2 and Ptgs2, was significantly increased by TiO₂ nanofibres, as well as by TiO₂ nanoparticles and crocidolite. This study indicates that TiO₂ nanofibres had significant toxic effects and, for most endpoints with the exception of pro-inflammatory changes, are more bio-active than TiO₂ nanoparticles, showing the relevance of shape in determining the toxicity of nanomaterials. Given that several toxic effects of TiO₂ nanofibres appear comparable to those observed with crocidolite, the possibility that they exert length dependent toxicity in vivo seems worthy of further investigation.     

Cerebral Blood Volume ASPECTS Is the Best Predictor of Clinical Outcome in Acute Ischemic Stroke: A Retrospective,Combined Semi-Quantitative and Quantitative Assessment

Introduction

The capability of CT perfusion (CTP) Alberta Stroke Program Early CT Score (ASPECTS) to predict outcome and identify ischemia severity in acute ischemic stroke (AIS) patients is still questioned.

Methods

62 patients with AIS were imaged within 8 hours of symptom onset by non-contrast CT, CT angiography and CTP scans at admission and 24 hours. CTP ASPECTS was calculated on the affected hemisphere using cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps by subtracting 1 point for any abnormalities visually detected or measured within multiple cortical circular regions of interest according to previously established thresholds. MTT-CBV ASPECTS was considered as CTP ASPECTS mismatch. Hemorrhagic transformation (HT), recanalization status and reperfusion grade at 24 hours, final infarct volume at 7 days and modified Rankin scale (mRS) at 3 months after onset were recorded.

Results

Semi-quantitative and quantitative CTP ASPECTS were highly correlated (p<0.00001). CBF, CBV and MTT ASPECTS were higher in patients with no HT and mRS≤2 and inversely associated with final infarct volume and mRS (p values: from p<0.05 to p<0.00001). CTP ASPECTS mismatch was slightly associated with radiological and clinical outcomes (p values: from p<0.05 to p<0.02) only if evaluated quantitatively. A CBV ASPECTS of 9 was the optimal semi-quantitative value for predicting outcome.

Conclusions

Our findings suggest that visual inspection of CTP ASPECTS recognizes infarct and ischemic absolute values. Semi-quantitative CBV ASPECTS, but not CTP ASPECTS mismatch, represents a strong prognostic indicator, implying that core extent is the main determinant of outcome, irrespective of penumbra size.     

Blockade of Thrombopoietin Reduces Organ Damage in Experimental Endotoxemia and Polymicrobial Sepsis

Background and Purpose

Thrombopoietin (TPO), a growth factor primarily involved in thrombopoiesis may also have a role in the pathophysiology of sepsis. In patients with sepsis, indeed, TPO levels are markedly increased, with disease severity being the major independent determinant of TPO concentrations. Moreover, TPO increases and correlates with ex vivo indices of platelet activation in patients with burn injury upon sepsis development, and may contribute to depress cardiac contractility in septic shock. Still, the role of TPO in sepsis pathophysiology remains controversial, given the protective role of TPO in other experimental disease models, for instance in doxorubicin-induced cardiotoxicity and myocardial ischemia/reperfusion injury. The aim of our study was to define the contribution of TPO in the development of organ damage induced by endotoxemia or sepsis, and to investigate the effects of inhibiting TPO in these conditions.

Methods

We synthesized a chimeric protein able to inhibit TPO, mTPOR-MBP, and studied its effect in two murine experimental models, acute endotoxemia and cecal ligation and puncture (CLP) model.

Results

In both models, TPO levels markedly increased, from 289.80±27.87 pg/mL to 465.60±45.92 pg/mL at 3 hours in the LPS model (P<0.01), and from 265.00±26.02 pg/mL to 373.70±26.20 pg/mL in the CLP model (P<0.05), respectively. Paralleling TPO levels, also platelet-monocyte aggregates increased, from 32.86±2.48% to 46.13±1.39% at 3 hours in the LPS model (P<0.01), and from 43.68±1.69% to 56.52±4.66% in the CLP model (P<0.05). Blockade of TPO by mTPOR-MBP administration reduced histological damage in target organs, namely lung, liver, and gut. In particular, neutrophil infiltration and lung septal thickening were reduced from a score of 1.86±0.34 to 0.60±0.27 (P<0.01) and from 1.43±0.37 to 0.40±0.16 (P<0.05), respectively, in the LPS model at 3 hours, and from a score of 1.75±0.37 to 0.38±0.18 (P<0.01) and from 1.25±0.31 to 0.13±0.13 (P<0.001), respectively, in the CLP model. Similarly, the number of hepatic microabscesses was decreased from 14.14±1.41 to 3.64±0.56 in the LPS model at 3 hours (P<0.001), and from 1.71±0.29 to 0.13±0.13 in the CLP model (P<0.001). Finally, the diameter of intestinal villi decreased from 90.69±3.95 μm to 70.74±3.60 μm in the LPS model at 3 hours (P<0.01), and from 74.29±4.29 μm to 57.50±1.89 μm in the CLP model (P<0.01). This protective effect was associated with the blunting of the increase in platelet-monocyte adhesion, and, on the contrary, with increased platelet-neutrophil aggregates in the circulation, which may be related to decreased neutrophil sequestration into the inflamed tissues. Conversely, circulating cytokine levels were not significantly changed, in both models, by mTPOR-MBP administration.

Conclusion

Our results demonstrate that TPO participates in the development of organ damage induced by experimental endotoxemia or polymicrobial sepsis via a mechanism involving increased platelet-leukocyte adhesion, but not cytokine release, and suggest that blocking TPO may be useful in preventing organ damage in patients affected by systemic inflammatory response or sepsis.     

Global 5-Hydroxymethylcytosine Levels Are Profoundly Reduced in Multiple Genitourinary Malignancies

Solid tumors are characterized by a plethora of epigenetic changes. In particular, patterns methylation of cytosines at the 5-position (5mC) in the context of CpGs are frequently altered in tumors. Recent evidence suggests that 5mC can get converted to 5-hydroxylmethylcytosine (5hmC) in an enzymatic process involving ten eleven translocation (TET) protein family members, and this process appears to be important in facilitating plasticity of cytosine methylation. Here we evaluated the global levels of 5hmC using a validated immunohistochemical staining method in a large series of clear cell renal cell carcinoma (n = 111), urothelial cell carcinoma (n = 55) and testicular germ cell tumors (n = 84) and matched adjacent benign tissues. Whereas tumor-adjacent benign tissues were mostly characterized by high levels of 5hmC, renal cell carcinoma and urothelial cell carcinoma showed dramatically reduced staining for 5hmC. 5hmC levels were low in both primary tumors and metastases of clear cell renal cell carcinoma and showed no association with disease outcomes. In normal testis, robust 5hmC staining was only observed in stroma and Sertoli cells. Seminoma showed greatly reduced 5hmC immunolabeling, whereas differentiated teratoma, embryonal and yolk sack tumors exhibited high 5hmC levels. The substantial tumor specific loss of 5hmC, particularly in clear cell renal cell carcinoma and urothelial cell carcinoma, suggests that alterations in pathways involved in establishing and maintaining 5hmC levels might be very common in cancer and could potentially be exploited for diagnosis and treatment.