Experimental Butchering of a Chimpanzee Carcass for Archaeological Purposes

Two archaeological assemblages from the Sierra de Atapuerca sites show evidence of anthropogenic cannibalism. These are the late Early Pleistocene level TD6-2 at Gran Dolina, and the Bronze Age level MIR4 in the Mirador Cave. Despite the chronological distance between these two assemblages, they share the common feature that the human remains exhibit a high frequency of anthropogenic modifications (cut marks, percussion pits and notches and peeling). This frequency could denote special treatment of bodies, or else be the normal result of the butchering process. In order to test these possibilities, we subjected a chimpanzee carcass to a butchering process. The processing was intensive and intended to simulate preparation for consumption. In doing this, we used several simple flakes made from quartzite and chert from quarries in the Sierra de Atapuerca. The skull, long bones, metapodials and phalanges were also fractured in order to remove the brain and bone marrow. As a result, about 40% of the remains showed some kind of human modification. The frequency, distribution and characteristics of these modifications are very similar to those documented on the remains of Homo antecessor from TD6-2. In case of the MIR4 assemblage, the results are similar except in the treatment of skulls. Our results indicate that high frequencies of anthropogenic modifications are common after an intensive butchering process intended to prepare a hominin body for consumption in different contexts (both where there was possible ritual behavior and where this was not the case and the modifications are not the result of special treatment).     

Re-examination and phylogeny of the genus Chondrostoma based on mitochondrial and nuclear data and the definition of 5 new genera

Previous molecular phylogenetic studies of the genus Chondrostoma (Cyprinidae: Leuciscinae) were unable to resolve the relationship among its major species groups. In this paper we present a phylogeny for this genus, based on five mitochondrial genes and the nuclear gene beta-actin, comprising a total of 4068 bp. Bayesian inference using all gene fragments yielded a fully resolved phylogeny, compatible with topologies obtained from individual fragments using maximum parsimony and minimum evolution. Mapping of morphological characters critical to the rasping feeding mode of most Chondrostoma species indicates that they evolved several times, and questions the use of these characters in the traditional definition of the genus. Our findings led us to the definition of the following new genera: Achondrostoma, Iberochondrostoma, Pseudochondrostoma, Protochondrostoma and Parachondrostoma. Our data contradict the hypothesis of a rapid radiation during Lago Mare phase, suggested by previous studies.     

Stroke pathophysiology: management challenges and new treatment advances

Stroke is the second leading cause of death and the first cause of lost disability-adjusted years in developed countries. During the past decade, new developments in thrombolytic therapy have led to the implementation of emergency intervention protocols for the treatment of ischemic stroke, replacing the widespread sense of therapeutic nihilism in the past. Treatment with rtPA has shown to be effective within the first 3 hours following stroke onset and the FDA and the European Medical Agency (EMEA) have approved its use. Acknowledging the urgency and intricacies of stroke, Stroke Units allow the monitoring of physiological parameters in the acute phase of stroke and are considered an important management tool that can significantly improve the quality of care provided to the patient. The concept of neuroprotective therapy for acute ischemic stroke to salvage tissue at risk and improve functional outcome is based on sound scientific principles and extensive preclinical animal studies demonstrating efficacy. However, most neuroprotective drugs in clinical trials have failed, possibly due to inadequate preclinical testing or flawed clinical development programs. Several new treatment strategies are under development and are being tested. This review is directed at understanding the management of acute ischemic stroke pathophysiology. We address the management challenges and new treatment advances by integrating the knowledge of possible pharmacological targets for acute ischemic stroke. We hope to shed new light upon the controversy surrounding the management of acute ischemic stroke in an attempt to elucidate why failed clinical trials continue to occur despite promising neuroprotective preclinical studies.     

Testing for the induction of anti-herbivory defences in four Portuguese macroalgae by direct and water-borne cues of grazing amphipods

Herbivory is a key factor in regulating plant biomass, thereby driving ecosystem performance. Algae have developed multiple adaptations to cope with grazers, including morphological and chemical defences. In a series of experiments we investigated whether several species of macroalgae possess anti-herbivore defences and whether these could be regulated to demand, i.e. grazing events. The potential of direct grazing on defence induction was assessed for two brown (Dictyopteris membranacea, Fucus vesiculosus) and two red seaweeds (Gelidium sesquipedale, Sphaerococcus coronopifolius) from São Rafael and Ria Formosa, Portugal. Bioassays conducted with live algal pieces and agar-based food containing lipophilic algal extracts were used to detect changes in palatability after exposure to amphipod attacks (=treatment phase). Fucus vesiculosus was the only species significantly reducing palatability in response to direct amphipod-attacks. This pattern was observed in live F. vesiculosus pieces and agar-based food containing a lipophilic extract, suggesting that lipophilic compounds produced during the treatment phase were responsible for the repulsion of grazers. Water-borne cues of grazed F. vesiculosus as well as non-grazing amphipods also reduced palatability of neighbouring conspecifics. However, this effect was only observed in live tissues of F. vesiculosus. This study is the first to show that amphipods, like isopods, are capable to induce anti-herbivory defences in F. vesiculosus and that a seasonally variable effectiveness of chemical defences might serve as a dynamic control in alga–herbivore interactions.     

A Pseudomonas putida cardiolipin synthesis mutant exhibits increased sensitivity to drugs related to transport functionality

Biological membranes have evolved different mechanisms to modify their composition in response to chemical stimuli in a process called 'homeoviscous adaptation'. Among these mechanisms, modifications in the ratio of saturated/unsaturated fatty acids and in cis/trans fatty acid isomers, cyclopropanation and changes in the phospholipids head group composition have been observed. To further understand the role of phospholipid head groups in solvent stress adaptation, we knocked out the cls (cardiolipin synthase) gene in Pseudomonas putida DOT-T1E. As expected, cls mutant membranes contained less cardiolipin than those of the wild-type strain. Although no significant growth rate defect was observed in the cls mutant compared with the wild-type strain, mutant cells were significantly smaller than the wild-type cells. The cls mutant was more sensitive to toluene shocks and to several antibiotics than the parental strain, suggesting either that the RND efflux pumps involved in the extrusion of these drugs were not working efficiently or that membrane permeability was altered in the mutant. Membranes of the cls mutant strain seemed to be more rigid than those of the parental strain, as observed by measurements of fluorescence polarization using the DPH probe, which intercalates into the membranes. Ethidium bromide is pumped out in Pseudomonas putida by at least one RND efflux pump involved in antibiotic and solvent resistance, and the higher rate of accumulation of ethidium bromide inside mutant cells indicated that functioning of the efflux pumps was compromised as a consequence of the alteration in phospholipid head group composition.     

Rab35 and glucocorticoids regulate APP and BACE1 trafficking to modulate Aβ production

Chronic stress and elevated glucocorticoids (GCs), the major stress hormones, are risk factors for Alzheimer’s disease (AD) and promote AD pathomechanisms, including overproduction of toxic amyloid-β (Aβ) peptides and intraneuronal accumulation of hyperphosphorylated Tau protein. The latter is linked to downregulation of the small GTPase Rab35, which mediates Tau degradation via the endolysosomal pathway. Whether Rab35 is also involved in Aβ overproduction remains an open question. Here, we find that hippocampal Rab35 levels are decreased not only by stress/GC but also by aging, another AD risk factor. Moreover, we show that Rab35 negatively regulates Aβ production by sorting amyloid precursor protein (APP) and β-secretase (BACE1) out of the endosomal network, where they interact to produce Aβ. Interestingly, Rab35 coordinates distinct intracellular trafficking steps for BACE1 and APP, mediated by its effectors OCRL and ACAP2, respectively. Finally, we demonstrate that Rab35 overexpression prevents the amyloidogenic trafficking of APP and BACE1 induced by high GC levels. These studies identify Rab35 as a key regulator of APP processing and suggest that its downregulation may contribute to stress-related and AD-related amyloidogenesis.Subject terms: Cellular neuroscience, Alzheimer''s disease     

Trophic niche changes associated with the eradication of invasive mammals in an insular lizard: an assessment using isotopes

Invasive species are a major threat to island biodiversity, and their eradications have substantially contributed to the conservation of island endemics. However, the consequences of eradications on the trophic ecology of native taxa are largely unexplored. Here, we used the eradication of invasive black rats Rattus rattus and European rabbits Oryctolagus cuniculus from the Berlenga Island, in the western coast of Portugal, as a whole-ecosystem experiment to investigate the effects of the eradication of invasive mammals on the trophic niche and body dimensions of the island-restricted Berlenga wall lizard Podarcis carbonelli berlengensis over a 2-year period. Our results suggest an expansion of the isotopic niche and an intensification of the sexual dimorphism of the lizard following mammal eradication. Additionally, we found considerable variability in isotopic niche across the island and detected evidence of sex-specific and season-modulated nutritional requirements of this threatened reptile. Our findings support that the eradication of 2 of the planet’s most problematic invasive vertebrates led to changes in the lizard trophic niche and sexual dimorphism in just 2 years. This suggests that the ecological pressures—for example, prey availability and habitat structure—to which lizards are exposed have substantially changed post-eradication. Our study emphasizes the scientific value of island eradications as experiments to address a wide range of ecological questions and adds to the increasing body of evidence supporting substantial conservation gains associated with these restoration interventions.     

Tumor immune cell clustering and its association with survival in African American women with ovarian cancer

New technologies, such as multiplex immunofluorescence microscopy (mIF), are being developed and used for the assessment and visualization of the tumor immune microenvironment (TIME). These assays produce not only an estimate of the abundance of immune cells in the TIME, but also their spatial locations. However, there are currently few approaches to analyze the spatial context of the TIME. Therefore, we have developed a framework for the spatial analysis of the TIME using Ripley’s K, coupled with a permutation-based framework to estimate and measure the departure from complete spatial randomness (CSR) as a measure of the interactions between immune cells. This approach was then applied to epithelial ovarian cancer (EOC) using mIF collected on intra-tumoral regions of interest (ROIs) and tissue microarrays (TMAs) from 160 high-grade serous ovarian carcinoma patients in the African American Cancer Epidemiology Study (AACES) (94 subjects on TMAs resulting in 263 tissue cores; 93 subjects with 260 ROIs; 27 subjects with both TMA and ROI data). Cox proportional hazard models were constructed to determine the association of abundance and spatial clustering of tumor-infiltrating lymphocytes (CD3+), cytotoxic T-cells (CD8+CD3+), and regulatory T-cells (CD3+FoxP3+) with overall survival. Analysis was done on TMA and ROIs, treating the TMA data as validation of the findings from the ROIs. We found that EOC patients with high abundance and low spatial clustering of tumor-infiltrating lymphocytes and T-cell subsets in their tumors had the best overall survival. Additionally, patients with EOC tumors displaying high co-occurrence of cytotoxic T-cells and regulatory T-cells had the best overall survival. Grouping women with ovarian cancer based on both cell abundance and spatial contexture showed better discrimination for survival than grouping ovarian cancer cases only by cell abundance. These findings underscore the prognostic importance of evaluating not only immune cell abundance but also the spatial contexture of the immune cells in the TIME. In conclusion, the application of this spatial analysis framework to the study of the TIME could lead to the identification of immune content and spatial architecture that could aid in the determination of patients that are likely to respond to immunotherapies.