Combination of diffusion tensor and functional magnetic resonance imaging during recovery from the vegetative state

Background  

The rate of recovery from the vegetative state (VS) is low. Currently, little is known of the mechanisms and cerebral changes that accompany those relatively rare cases of good recovery. Here, we combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to study the evolution of one VS patient at one month post-ictus and again twelve months later when he had recovered consciousness.     

Deacetylase activity is required for STAT5-dependent GM-CSF functional activity in macrophages and differentiation to dendritic cells

After interaction with its receptor, GM-CSF induces phosphorylation of the beta-chain in two distinct domains in macrophages. One induces activation of mitogen-activated protein kinases and the PI3K/Akt pathway, and the other induces JAK2-STAT5. In this study we describe how trichostatin A (TSA), which inhibits deacetylase activity, blocks JAK2-STAT5-dependent gene expression but not the expression of genes that depend on the signal transduction induced by the other domain of the receptor. TSA treatment inhibited the GM-CSF-dependent proliferation of macrophages by interfering with c-myc and cyclin D1 expression. However, M-CSF-dependent proliferation, which requires ERK1/2, was unaffected. Protection from apoptosis, which involves Akt phosphorylation and p21(waf-1) expression, was not modified by TSA. GM-CSF-dependent expression of MHC class II molecules was inhibited because CIITA was not induced. The generation of dendritic cells was also impaired by TSA treatment because of the inhibition of IRF4, IRF2, and RelB expression. TSA mediates its effects by preventing the recruitment of RNA polymerase II to the promoter of STAT5 target genes and by inhibiting their expression. However, this drug did not affect STAT5A or STAT5B phosphorylation or DNA binding. These results in GM-CSF-treated macrophages reveal a relationship between histone deacetylase complexes and STAT5 in the regulation of gene expression.     

Sepsis induces DNA fragmentation in rat skeletal muscle

Recent studies have demonstrated the activation of skeletal muscle DNA fragmentation in some catabolic conditions. In an attempt to elucidate if sepsis (a catabolic state) was also associated with muscle apoptosis, sepsis was induced by cecal ligation and puncture, and the results clearly show an induction of DNA fragmentation in gastrocnemius muscle following the induction of the septic state. Administration of rolipram (an inhibitor of tumour necrosis factor-a (TNF-alpha) synthesis) to septic rats clearly prevented the increased DNA fragmentation, suggesting that TNF-alpha is involved in the activation of the apoptotic events in septic rat skeletal muscle.     

Trophic niche overlap between round sardinella (Sardinella aurita) and sympatric pelagic fish species in the Western Mediterranean

The northward expansion of round sardinella (Sardinella aurita) in the Mediterranean Sea, together with declines and fluctuations in biomass and landings of European sardine (Sardina pilchardus) and anchovy (Engraulis encrasicolus) observed in recent decades, may suggest potential inter‐specific competition in the pelagic domain. The coexistence of sympatric zooplanktivorous fish species might therefore be exposed in part to trophic niche overlap and competition for food. Combining visual diet characterization under the microscope with DNA metabarcoding from stomach contents of fish collected in spring results show that predation on relatively large krill is equally important for sardinella than for the other two niche overlapping species. Furthermore, an important overlap is found in their isotopic niche, especially with anchovy, using nitrogen (δ¹⁵N) and carbon (δ¹³C) stable isotopes in muscle tissue. In fact, the three fish species are able to feed effectively in the whole prey size spectrum available during the sampled season, from the smallest diatoms and copepods to the larger prey (i.e., decapods and euphausiids), including fish larvae. Moreover, effective predation upon other large prey like siphonophores, which is observed only when multi‐proxy analyses in stomach contents are applied, might also be relevant in the diet of sardinella. The overlapping diet composition in spring, together with the effective use of food resource by sardinella, can be of special interest in potential future scenarios with warmer water temperature leading to lower zooplankton and/or higher jellyfish availability, where sardinella may take advantage over other species due to its feeding plasticity.     

Detection of a population replacement at the Classic-Postclassic transition in Mexico

The Mexica Empire reached an outstanding social, economic and politic organization among Mesoamerican civilizations. Even though archaeology and history provide substantial information about their past, their biological origin and the demographic consequences of their settlement in the Central Valley of Mexico remain unsolved. Two main hypotheses compete to explain the Mexica origin: a social reorganization of the groups already present in the Central Valley after the fall of the Classic centres or a population replacement of the Mesoamerican groups by migrants from the north and the consequent setting up of the Mexica society. Here, we show that the main changes in the facial phenotype occur during the Classic-Postclassic transition, rather than in the rise of the Mexica. Furthermore, Mexica facial morphology seems to be already present in the early phases of the Postclassic epoch and is not related to the northern facial pattern. A combination of geometric morphometrics with Relethford-Blangero analyses of within- versus among-group variation indicates that Postclassic groups are more variable than expected. This result suggests that intense gene exchange was likely after the fall of the Classic and maybe responsible for the Postclassic facial phenotype. The source population for the Postclassic groups could be located somewhere in western Mesoamerica, since North Mexico and Central Mesoamerican Preclassic and Classic groups are clearly divergent from the Postclassic ones. Similarity among Preclassic and Classic groups and those from Aridoamerica could be reflecting the ancestral phenotypic pattern characteristic of the groups that first settled Mesoamerica.     

Study of lactoferrin gene expression in human and mouse adipose tissue,human preadipocytes and mouse 3T3-L1 fibroblasts. Association with adipogenic and inflammatory markers

Lactoferrin is considered an epithelial protein present in different gland secretions. Administration of exogenous lactoferrin is also known to modulate adipogenesis and insulin action in human adipocytes. Here, we aimed to investigate lactoferrin gene expression (real-time polymerase chain reaction) and protein (enzyme-linked immunosorbent assay) levels in human (n=143) and mice adipose tissue samples, in adipose tissue fractions and during human preadipocyte and 3T3-L1 cell line differentiation, evaluating the effects of inducers (rosiglitazone) and disruptors (inflammatory factors) of adipocyte differentiation. Lactoferrin (LTF) gene and protein were detectable at relatively high levels in whole adipose tissue and isolated adipocytes in direct association with low-density lipoprotein-related protein 1 (LRP1, its putative receptor). Obese subjects with type 2 diabetes and increased triglycerides had the lowest levels of LTF gene expression in subcutaneous adipose tissue. Specifically, LTF gene expression was significantly increased in adipocytes, mainly from lean subjects, increasing during differentiation in parallel to adipogenic genes and gene markers of lipid droplets. The induction or disruption of adipogenesis led to concomitant changes (increase and decrease, respectively) of lactoferrin levels during adipocyte differentiation also in parallel to gene markers of adipogenesis and lipid droplet development. The administration of lactoferrin led to autopotentiated increased expression of the LTF gene. The decreased lactoferrin mRNA levels in association with obesity and diabetes were replicated in mice adipose tissue. In conclusion, this is the first observation, to our knowledge, of lactoferrin gene expression in whole adipose tissue and isolated adipocytes, increasing during adipogenesis and suggesting a possible contribution in adipose tissue physiology through LRP1.     

Side effects of chaperone gene co-expression in recombinant protein production

Insufficient availability of molecular chaperones is observed as a major bottleneck for proper protein folding in recombinant protein production. Therefore, co-production of selected sets of cell chaperones along with foreign polypeptides is a common approach to increase the yield of properly folded, recombinant proteins in bacterial cell factories. However, unbalanced amounts of folding modulators handling folding-reluctant protein species might instead trigger undesired proteolytic activities, detrimental regarding recombinant protein stability, quality and yield. This minireview summarizes the most recent observations of chaperone-linked negative side effects, mostly focusing on DnaK and GroEL sets, when using these proteins as folding assistant agents. These events are discussed in the context of the complexity of the cell quality network and the consequent intricacy of the physiological responses triggered by protein misfolding.     

Cultural Diffusion Was the Main Driving Mechanism of the Neolithic Transition in Southern Africa

It is well known that the Neolithic transition spread across Europe at a speed of about 1 km/yr. This result has been previously interpreted as a range expansion of the Neolithic driven mainly by demic diffusion (whereas cultural diffusion played a secondary role). However, a long-standing problem is whether this value (1 km/yr) and its interpretation (mainly demic diffusion) are characteristic only of Europe or universal (i.e. intrinsic features of Neolithic transitions all over the world). So far Neolithic spread rates outside Europe have been barely measured, and Neolithic spread rates substantially faster than 1 km/yr have not been previously reported. Here we show that the transition from hunting and gathering into herding in southern Africa spread at a rate of about 2.4 km/yr, i.e. about twice faster than the European Neolithic transition. Thus the value 1 km/yr is not a universal feature of Neolithic transitions in the world. Resorting to a recent demic-cultural wave-of-advance model, we also find that the main mechanism at work in the southern African Neolithic spread was cultural diffusion (whereas demic diffusion played a secondary role). This is in sharp contrast to the European Neolithic. Our results further suggest that Neolithic spread rates could be mainly driven by cultural diffusion in cases where the final state of this transition is herding/pastoralism (such as in southern Africa) rather than farming and stockbreeding (as in Europe).     

Enhanced response to antibody binding in engineered beta-galactosidase enzymatic sensors

Peptide display on solvent-exposed surfaces of engineered enzymes allows them to respond to anti-peptide antibodies by detectable changes in their enzymatic activity, offering a new principle for biosensor development. In this work, we show that multiple peptide insertion in the vicinity of the Escherichia coli beta-galactosidase active site dramatically increases the enzyme responsiveness to specific anti-peptide antibodies. The modified enzymes HD7872A and HT7278CA, carrying eight and 12 copies respectively of a foot-and-mouth disease peptide per enzyme molecule, show antibody-mediated activation factors higher than those previously observed in the first generation enzymatic sensors, for HT7278CA being close to 400%. The analysis of the signal transduction process with multiple inserted proteins strongly suggests a new, non-exclusive mechanism of enzymatic regulation in which the target proteins might be stabilised by the bound antibody, extending the enzyme half-life and consequently enhancing the signal-background ratio. In addition, the tested sensors are differently responsive to sera from immune farm animals, depending on the antigenic similarity between the B-cell epitopes in the immunising virus and those in the peptide used as sensing element on the enzyme surface. Altogether, these results point out the utility of these enzymatic biosensors for a simple diagnosis of foot-and-mouth disease in an extremely fast homogeneous assay.