The Neanderthal patellae from Krapina (Croatia): A comparative investigation of their endostructural conformation and distinctive features compared to the extant human condition

Objectives

The Neanderthal patella differs from that of extant humans by being thicker anteroposteriorly and by having more symmetric medial and lateral articular facets. However, it is still unclear to what extent these differences affect knee kinesiology. We aim at assessing the endostructural conformation of Neanderthal patellae to reveal functionally related mechanical information comparatively to the extant human condition. In principle, we expect that the Neanderthal patella (i) shows a higher amount of cortical bone and (ii) a trabecular network organization distinct from the extant human condition.

Materials and Methods

By using micro-focus X-ray tomography, we characterized the endostructure of six adult patellae from the OIS 5e Neanderthal site of Krapina, Croatia, the largest assemblage of human fossil patellae assessed so far, and compared their pattern to the configuration displayed by a sample of 22 recent humans.

Results and Discussion

The first expectation is rejected, indicating that the patellar bone might have not followed the trend of generalized gracilization of the human postcranial skeleton occurred through the Upper Pleistocene. The second prediction is at least partially supported. In Krapina the trabecular network differs from the comparative sample by showing a higher medial density and by lacking a proximal reinforcement. Such conformation indicates similar load patterns exerted in Neanderthals and extant humans by the vastus lateralis, but not by the vastus medialis, with implications on the mediolateral stabilization of the knee joint. However, the patterns of structural variation of the patellar network remain to be assessed in other Neanderthal samples.

     

The Use of Biomarker Expression to Characterize Neoplastic Processes

Biomarkers have been used by pathologists to aid the diagnosis of tumors for almost three decades. Their use has resulted in the re-evaluation and reclassification of several types of tumors. Currently, biomarkers are required to differentiate certain specific tumors with similar histologic patterns. Additional uses of biomarkers in the characterization of neoplastic processes are discussed including their use in prognosis, detecting early neoplastic processes, identifying tumor recurrence, measuring the effectiveness of various therapies (surrogate end point biomarkers), and identifying targets for novel therapies including immunotherapy and gene therapy. We propose that these newer uses of biomarkers will be just as important to pathology in the future as the uses of biomarkers in diagnosis have been over the past two decades.     

Binding studies of NADPH to NADP-specific L-glutamate dehydrogenase from Saccharomyces cerevisiae.

Optical characteristics of enzyme-reduced coenzyme complexes of yeast NADP-specific glutamate dehydrogenase have been investigated in the presence and absence of product (L-glutamate) and in the presence or absence of phosphate. The phosphate effect, pointed out in a previous work, is found again: inorganic phosphate (Pi) destabilizes the binary complex (E - NADPH), the dissociation constant of which is equal to 14 muM, a value much higher than that determined in Tris-HCl buffer: Kd = 0.9 muM. Concerning the role of phosphate some assumptions are drawn up with respect to a similar behaviour of Pi toward yeast glutamate dehydrogenase and ADP toward the beef liver enzyme. In the same way, L-glutamate induces a stabilization of the binary complex; this latter effect is unchanged in the presence of phosphate, yet it is less marked than in the case of beef liver glutamate dehydrogenase. Protein fluorescence, nucleotide fluorescence and circular dichroism measurements allowed the determination of three identical and independent NADPH binding sites per hexameric active unit. In analogy with beef liver enzyme, it seems that yeast glutamate dehydrogenase is a good model to study anticooperativity in ligand binding.     

Apoptosis mapping in space and time of 3D tumor ecosystems reveals transmissibility of cytotoxic cancer death

The emerging tumor-on-chip (ToC) approaches allow to address biomedical questions out of reach with classical cell culture techniques: in biomimetic 3D hydrogels they partially reconstitute ex vivo the complexity of the tumor microenvironment and the cellular dynamics involving multiple cell types (cancer cells, immune cells, fibroblasts, etc.). However, a clear bottleneck is the extraction and interpretation of the rich biological information contained, sometime hidden, in the cell co-culture videos. In this work, we develop and apply novel video analysis algorithms to automatically measure the cytotoxic effects on human cancer cells (lung and breast) induced either by doxorubicin chemotherapy drug or by autologous tumor-infiltrating cytotoxic T lymphocytes (CTL). A live fluorescent dye (red) is used to selectively pre-stain the cancer cells before co-cultures and a live fluorescent reporter for caspase activity (green) is used to monitor apoptotic cell death. The here described open-source computational method, named STAMP (spatiotemporal apoptosis mapper), extracts the temporal kinetics and the spatial maps of cancer death, by localizing and tracking cancer cells in the red channel, and by counting the red to green transition signals, over 2–3 days. The robustness and versatility of the method is demonstrated by its application to different cell models and co-culture combinations. Noteworthy, this approach reveals the strong contribution of primary cancer-associated fibroblasts (CAFs) to breast cancer chemo-resistance, proving to be a powerful strategy to investigate intercellular cross-talks and drug resistance mechanisms. Moreover, we defined a new parameter, the ‘potential of death induction’, which is computed in time and in space to quantify the impact of dying cells on neighbor cells. We found that, contrary to natural death, cancer death induced by chemotherapy or by CTL is transmissible, in that it promotes the death of nearby cancer cells, suggesting the release of diffusible factors which amplify the initial cytotoxic stimulus.     

Does body posture influence hand preference in an ancestral primate model?

Background  

The origin of human handedness and its evolution in primates is presently under debate. Current hypotheses suggest that body posture (postural origin hypothesis and bipedalism hypothesis) have an important impact on the evolution of handedness in primates. To gain insight into the origin of manual lateralization in primates, we studied gray mouse lemurs, suggested to represent the most ancestral primate condition. First, we investigated hand preference in a simple food grasping task to explore the importance of hand usage in a natural foraging situation. Second, we explored the influence of body posture by applying a forced food grasping task with varying postural demands (sit, biped, cling, triped).     

Intranasal vaccination with a lentiviral vector protects against SARS-CoV-2 in preclinical animal models

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