Cranial endocast of Anagale gobiensis (Anagalidae) and its implications for early brain evolution in Euarchontoglires

Anagalids are an extinct group of primitive mammals from the Asian Palaeogene thought to be possible basal members of Glires. Anagalid material is rare, with only a handful of crania known. Here we describe the first virtual endocast of an anagalid, based on the holotype of Anagale gobiensis (AMNH 26079; late Eocene, China), which allows for comparison with published endocasts from fossil members of modern euarchontogliran lineages (i.e. primates, rodents, lagomorphs). The endocast displays traits often observed in fossorial mammals, such as relatively small petrosal lobules and a low neocortical ratio, which would be consistent with previous inferences about use of subterranean food sources based on heavy dental wear. In fact, Anagale gobiensis has the lowest neocortical ratio yet recorded for a euarchontogliran. This species was olfaction-driven, based on the relatively large olfactory bulbs and laterally expansive palaeocortex. The endocast supports previous inferences that relatively large olfactory bulbs, partial midbrain exposure and low encephalization quotient are ancestral for Euarchontoglires, although the likely fossorial adaptations of Anagale gobiensis may also partly explain these traits. While Anagale gobiensis is a primitive mammal in many aspects, some of its derived endocranial traits point towards a new, different trajectory of brain evolution within Euarchontoglires.     

Hematopoietic progenitor cell liabilities and alarmins S100A8/A9‐related inflammaging associate with frailty and predict poor cardiovascular outcomes in older adults

Frailty affects the physical, cognitive, and social domains exposing older adults to an increased risk of cardiovascular disease and death. The mechanisms linking frailty and cardiovascular outcomes are mostly unknown. Here, we studied the association of abundance (flow cytometry) and gene expression profile (RNAseq) of stem/progenitor cells (HSPCs) and molecular markers of inflammaging (ELISA) with the cardiorespiratory phenotype and prospective adverse events of individuals classified according to levels of frailty. Two cohorts of older adults were enrolled in the study. In a cohort of pre‐frail 35 individuals (average age: 75 years), a physical frailty score above the median identified subjects with initial alterations in cardiorespiratory function. RNA sequencing revealed S100A8/A9 upregulation in HSPCs from the bone marrow (>10‐fold) and peripheral blood (>200‐fold) of individuals with greater physical frailty. Moreover higher frailty was associated with increased alarmins S100A8/A9 and inflammatory cytokines in peripheral blood. We then studied a cohort of 104 more frail individuals (average age: 81 years) with multidomain health deficits. Reduced levels of circulating HSPCs and increased S100A8/A9 concentrations were independently associated with the frailty index. Remarkably, low HSPCs and high S100A8/A9 simultaneously predicted major adverse cardiovascular events at 1‐year follow‐up after adjustment for age and frailty index. In conclusion, inflammaging characterized by alarmin and pro‐inflammatory cytokines in pre‐frail individuals is mirrored by the pauperization of HSPCs in frail older people with comorbidities. S100A8/A9 is upregulated within HSPCs, identifying a phenotype that associates with poor cardiovascular outcomes.     

Reactivation of human polyomavirus JC in patients affected by psoriasis vulgaris and psoriatic arthritis and treated with biological drugs: Preliminary results

Psoriasis vulgaris (PsV) and psoriatic arthritis (PSA) are inter‐related heritable inflammatory skin diseases. Psoriatic lesions develop as a result of abnormal immune responses, hyperproliferation and altered differentiation of keratinocytes, and a notable subset of psoriatic patients develops PsA, characterized by joints inflammation. Recently, biological drugs were introduced to treat these diseases. However, this therapy has already been associated with the development of serious life‐threatening infections, such as the reactivation of human polyomavirus JC (JCV), responsible for the progressive multifocal leukoencephalopathy (PML), a lethal demyelinating disease caused by oligodendrocytes lytic infection. Therefore, the aims of our study were the investigation of the possible JCV reactivation in PsV and PsA patients treated with adalimumab, etanercept, and methotrexate, performing quantitative real‐time PCR in sera and skin biopsies at the time of recruitment (T0) and after 3 (T3) and 6 (T6) months of treatment, and the sequencing analysis of the JCV non‐coding control region (NCCR). We found JCV DNA in 5/15 PsV patients and in 2/15 PsA patients and JCV NCCR sequence analysis always showed a structure similar to non‐pathogenic CY archetype, with random occurrence of a few irrelevant point mutations. Nevertheless the poor number of patients analyzed, our preliminary data can pave the way for taking into account that the follow‐up of JCV DNA detection and the JCV NCCR sequence analysis in psoriatic patients may be important to evaluate the risk of PML onset, considering that patients affected by autoimmune diseases and treated with biologics continue to rise. J. Cell. Physiol. 227: 3796–3802, 2012. © 2012 Wiley Periodicals, Inc.     

SV40 T antigen and telomerase are required to obtain immortalized human adult bone cells without loss of the differentiated phenotype.

In most human primary bone cells, SV40 T-antigen expression was able to expand life span for a few passages before cells undergo growth arrest, described as crisis. In this study, telomerase activity was reconstituted in human osteoblast precursors (hPOB cells) and marrow stromal cells (Saka cells) transformed with the SV40 T antigen. Bone cells with telomerase activity were able to bypass crisis and show unlimited life span. Despite chromosomal aberrations observed in hPOB-tert cells, these immortalized precursors were able to differentiate into osteoblasts like precrisis hPOB cells. Saka-tert cells enhanced the formation of human osteoclast-like cells in a similar manner as Saka cells. These results demonstrate that reconstitution of telomerase activity in transformed SV40 T-antigen human osteoblast precursors or marrow stromal cells leads to the generation of immortalized cells with a preserved phenotype.     

Ultradian chronomodulation by melatonin of a Placebo effect upon human killer cell activity

The effect of melatonin injection evaluated earlier with respect to placebo-treated controls is reevaluated, also with reference to spontaneous changes in natural killer cell activity. This effect consists, first, of stimulation of natural killer cell activity over and above any changes brought about by placebo (saline). After 6 h, the melatonin effect appears to be an inhibition as compared to values from placebo-treated subjects, or no effect as compared to values from untreated subjects. In this case, amplification and attenuation of the placebo effect by melatonin are found within the relatively short span of 1/4 of a day, rather than within a day or a week. An ultradian 'feed-sideward' by melatonin may be aligned with the corresponding previously reported circadian and infradian chronomodulation.     

The Phylogenesis of Language: The Grammar of Gestures and the Manipulation of Words

Current studies on the origin of language clearly show the necessity to go beyond the debate of nature vs. culture in order to pursue an interdisciplinary perspective. The convergence of researches carried out in different fields – neurobiology, palaeoanthropology and linguistics – outlines in a rather clear and convincing framework the strong link between language and motility. Various sources of evidence demonstrate how the mechanisms of culture acquisition and transmission – imitation, language and dexterity – refer back to the same cerebral structures. Moreover, both the motor and the linguistic systems show an identical multileveled basic structure that allows humans high levels of expressiveness. Actions such as the production of tools or the throwing of objects, connected to the very first human behaviours, emerge through space-time concatenations related to the linguistic logic. The hypothesis of a coevolution of language and motor patterns and of a very remote origin of verbal communication is thus debated.     

Simultaneous cytofluorometric analysis for the expression of cytoplasmic antigens and DNA content in CD3- human thymocytes

We describe a method of two-color immunofluorescence staining which allows the simultaneous analysis of both cytoplasmic antigens and cell entry into the S/G2/M cell cycle phases. This analysis was performed on CD3(-)-activated thymocytes obtained from either highly purified CD1-CD3-CD4-CD8- cells or fresh thymus cell suspensions, stimulated with low doses of phorbol-12 myristate-13 acetate (0.5 ng/ml) and interleukin-2. On the 14th day under these culture conditions about 90% of thymocytes did not express CD3 antigen on the cell surface. CD3- cells were further purified by cell sorting, fixed in paraformaldehyde, and permeabilized with Nonidet-P40. Then these thymocytes were stained by indirect immunofluorescence with monoclonal antibodies identifying T cell-specific molecules (CD3, CD2, CD28, TCR alpha/beta, and TCR gamma/delta) and analyzed for DNA content. Interestingly, both CD3 and CD28 antigens were detectable in the cytoplasm of most cells (greater than 80%). Further, the majority of the thymocytes which had entered the S/G2/M phases of the cell cycle (20%) expressed intracellular CD3 and CD28 molecules and reacted with the anti-beta framework beta F1 monoclonal antibody. The relationship between the appearance of CD3 and other T cell markers in the cytoplasm, the cell cycle entry, and the thymocyte development is discussed.     

Preparation of (+)- and (−)-1,2-dimethyl-3-pyrrolidone and stability studies

1,2-Dimethyl-3-pyrrolidone is an important intermediate in the synthesis of cycloalkylaminonaphthalenic analgesics. The optical resolution of this compound with L- and D-tartaric acids is described and the behaviour of the diastereomeric tartrates and of the enantiomers in solution was investigated by NMR spectroscopy and polarimetric analysis. Tautomeric equilibria involving C4 and C2 atoms, which are responsible for the instability of the compound, are demonstrated. Theoretical studies of conformational analysis were also made in order to define the relationships between the stability of the conformers of 1,2-dimethyl-3-pyrrolidone and its structural features. © 1995 Wiley-Liss, Inc.     

Particular ultrastructural aspects of human Paneth's cells]

Our research is about the ultrastructural aspects of Paneth cells obtained from human jejunal mucosa. The cells appear columnar in shape and show a roundish nucleus; their cytoplasm is characterized by a great amount of R.E.R. and by typical large granules in sopranuclear position. Our results confirm those previously described by other authors about the morphology of Paneth cells. In our specimens we have found moreover a variable number of particular cytoplasmic structures; these may show a fibrillar or granular matrix and are always surrounded by a membrane.