Pervasive cranial allometry at different anatomical scales and variational levels in extant armadillos

Allometry, i.e., morphological variation correlated with size, is a major pattern in organismal evolution. Since size varies both within and among species, allometry occurs at different variational levels. However, the variability of allometric patterns across levels is poorly known since its evaluation requires extensive comparative studies. Here, we implemented a 3D geometric morphometric approach to investigate cranial allometry at three main variational levels—static, ontogenetic, and evolutionary—and two anatomical scales—entire cranium and cranial subunits—based on a dense intra- and interspecific sampling of extant armadillo diversity. While allometric trajectories differ among distantly related species, they hardly do so among sister families. This suggests that phylogenetic distance plays an important role in explaining allometric divergences. Beyond trajectories, our analyses revealed pervasive allometric shape changes shared across variational levels and anatomical scales. At the entire cranial scale, craniofacial allometry (relative snout elongation and braincase reduction) is accompanied notably by variations of nuchal crests and postorbital constriction. Among cranial subunits, the distribution of allometry was highly heterogeneous, with the frontal and petrosal bones showing the most pervasive shape changes, some of which were undetected at a more global scale. Evidence of widespread and superimposed allometric variations raises questions on their determinants and anatomical correlates and demonstrates the critical role of allometry in morphological evolution

TPT1/TCTP-regulated pathways in phenotypic reprogramming

Evolutionary conserved and pleiotropic, the TPT1/TCTP gene (translationally controlled tumor protein, also called HRF, fortilin), encodes a highly structured mRNA shielded by ribonucleoproteins and closely resembling viral particles. This mRNA activates, as do viruses, protein kinase R (PKR). The TPT1/TCTP protein is structurally similar to mRNA-helicases and MSS4. TPT1/TCTP has recently been identified as a prognostic factor in breast cancer and a critical regulator of the tumor suppressor p53 and of the cancer stem cell (SC) compartment. Emerging evidence indicates that TPT1/TCTP is key to phenotypic reprogramming, as shown in the process of tumor reversion and possibly in pluripotency. We provide here an overview of these diverse functions of TPT1/TCTP

Biomechanical evolution of solid bones in large animals: a microanatomical investigation

International audienc

HAEMATOLOGICAL PARAMETERS IN H UMAN I MMUNODEFICIENCY V IRUS POSITIVE INDIVIDUALS ON DIFFERENT HAART REGIMEN .

Highly active antiretroviral viral therapy (HAART), a combination of three antiretrovirals from at least two drug classes for optimization of hindrance to HIV replication has g reatly increased life expectance. There however, exist numerous of these combinations and thus the questions of which is the best HAART combination with respect to the individual’s haematological status. To investigate this, blood samples were collected fr om 231 retropositive subjects on six different HAART combinations at least six months after HAART commencement, assayed for CD4 and some haematological parameters using cyflow and sysmex(KX - 21) autoanalysier. Baseline data was accessed from the LAMIS data base. The difference between baseline and values after HAART was taken and statistically compared. HAART evaluated includes, Combivir(NVP), Combivir(EFV), Truvada(NVP), Truvada(EFV), Lanten(NVP) and Lanten(EFV). The difference in the parameters assayed a re: CD4(cellmm - 3 ): 154, 205, 172, 206, 262, and 230(P=0.478). Haemoglobin(gdl - 1): - 0.78, - 0.73, 2.35, 1.48, 1.11 and 1.27(P=0.010). PCV(%): - 2.34, - 2.19, 7.65, 7.02, 3.36 and 3.12(P=0.0001). WBC(10 3 μl - 1 ): - 1.19, - 1.02, - 0.37, 0.06, 1.14 and - 0.63(P=0.001) . Neutrophil(%): - 1.51, - 1.83, 3.87, 2.07, 2.71, 2.71 and 1.97(P=0.868). Lymphocyte(%): - 4.26, - 2.87, - 1.45, - 0.19, 2.36 and 3.40(P=0.790). Eosinophil(%): - 0.41, 0.14, - 2.65, 0.14, - 0.46 and 0.12(P=0.094). Platelet(10 3 μl - 1 ): - 49, - 39, - 53, - 53, - 47 and - 35 (P=0.931). The Zidovudine based combinations showed anaemic tendencies; Nevirapen based combinations showed Eosinopenic tendencies. All HAART used induced good immunologic responses along with thrombocytopenic tendencies. The data generated was however ins ufficient to discriminate one combination as being better than the other, rather it was observed that the haematological profile of clients must be well considered when selecting HAAR

Exosome-Related Multi-Pass Transmembrane Protein TSAP6 Is a Target of Rhomboid Protease RHBDD1-Induced Proteolysis

We have previously reported that rhomboid domain containing 1 (RHBDD1), a mammalian rhomboid protease highly expressed in the testis, can cleave the Bcl-2 protein Bik. In this study, we identified a multi-pass transmembrane protein, tumor suppressor activated pathway-6 (TSAP6) as a potential substrate of RHBDD1. RHBDD1 was found to induce the proteolysis of TSAP6 in a dose- and activity-dependent manner. The cleavage of TSAP6 was not restricted to its glycosylated form and occurred in three different regions. In addition, mass spectrometry and mutagenesis analyses both indicated that the major cleavage site laid in the C-terminal of the third transmembrane domain of TSAP6. A somatic cell knock-in approach was used to genetically inactivate the endogenous RHBDD1 in HCT116 and RKO colon cancer cells. Exosome secretion was significantly elevated when RHBDD1 was inactivated in the two cells lines. The increased exosome secretion was verfied through the detection of certain exosomal components, including Tsg101, Tf-R, FasL and Trail. In addition, the elevation of exosome secretion by RHBDD1 inactivation was reduced when TSAP6 was knocked down, indicating that the role of RHBDD1 in regulating exosomal trafficking is very likely to be TSAP6-dependent. We found that the increase in FasL and Trail increased exosome-induced apoptosis in Jurkat cells. Taken together, our findings suggest that RHBDD1 is involved in the regulation of a nonclassical exosomal secretion pathway through the restriction of TSAP6

Distinct expression patterns of the E3 ligase SIAH-1 and its partner Kid/KIF22 in normal tissues and in the breast tumoral processes

SIAH proteins are the human members of an highly conserved family of E3 ubiquitin ligases. Several data suggest that SIAH proteins may have a role in tumor suppression and apoptosis. Previously, we reported that SIAH-1 induces the degradation of Kid (KIF22), a chromokinesin protein implicated in the normal progression of mitosis and meiosis, by the ubiquitin proteasome pathway. In human breast cancer cells stably transfected with SIAH-1, Kid/KIF22 protein level was markedly reduced whereas, the Kid/KIF22 mRNA level was increased. This interaction has been further elucidated through analyzing SIAH and Kid/KIF22 expression in both paired normal and tumor tissues and cell lines. It was observed that SIAH-1 protein is widely expressed in different normal tissues, and in cells lines but showing some differences in western blotting profiles. Immunofluorescence microscopy shows that the intracellular distribution of SIAH-1 and Kid/KIF22 appears to be modified in human tumor tissues compared to normal controls. When mRNA expression of SIAH-1 and Kid/KIF22 was analyzed by real-time PCR in normal and cancer breast tissues from the same patient, a large variation in the number of mRNA copies was detected between the different samples. In most cases, SIAH-1 mRNA is decreased in tumor tissues compared to their normal counterparts. Interestingly, in all breast tumor tissues analyzed, variations in the Kid/KIF22 mRNA levels mirrored those seen with SIAH-1 mRNAs. This concerted variation of SIAH-1 and Kid/KIF22 messengers suggests the existence of an additional level of control than the previously described protein-protein interaction and protein stability regulation. Our observations also underline the need to re-evaluate the results of gene expression obtained by qRT-PCR and relate it to the protein expression and cellular localization when matched normal and tumoral tissues are analyzed

KSHV Reactivation from Latency Requires Pim-1 and Pim-3 Kinases to Inactivate the Latency-Associated Nuclear Antigen LANA

Host signal-transduction pathways are intimately involved in the switch between latency and productive infection of herpes viruses. As with other herpes viruses, infection by Kaposi's sarcoma herpesvirus (KSHV) displays these two phases. During latency only few viral genes are expressed, while in the productive infection the virus is reactivated with initiation of extensive viral DNA replication and gene expression, resulting in production of new viral particles. Viral reactivation is crucial for KSHV pathogenesis and contributes to the progression of KS. We have recently identified Pim-1 as a kinase reactivating KSHV upon over-expression. Here we show that another Pim family kinase, Pim-3, also induces viral reactivation. We demonstrate that expression of both Pim-1 and Pim-3 is induced in response to physiological and chemical reactivation in naturally KSHV-infected cells, and we show that they are required for KSHV reactivation under these conditions. Furthermore, our data indicate that Pim-1 and Pim-3 contribute to viral reactivation by phosphorylating the KSHV latency-associated nuclear antigen (LANA) on serine residues 205 and 206. This counteracts the LANA–mediated repression of the KSHV lytic gene transcription. The identification of Pim family kinases as novel cellular regulators of the gammaherpesvirus life cycle facilitates a deeper understanding of virus–host interactions during reactivation and may represent potential novel targets for therapeutic intervention

Loss of p53 results in protracted electrographic seizures and development of an aggravated epileptic phenotype following status epilepticus

The p53 tumor suppressor is a multifunctional protein, which regulates cell cycle, differentiation, DNA repair and apoptosis. Experimental seizures up-regulate p53 in the brain, and acute seizure-induced neuronal death can be reduced by genetic deletion or pharmacologic inhibition of p53. However, few long-term functional consequences of p53 deficiency have been explored. Here, we investigated the development of epilepsy triggered by status epilepticus in wild-type and p53-deficient mice. Analysis of electroencephalogram (EEG) recordings during status epilepticus induced by intra-amygdala kainic acid (KA) showed that seizures lasted significantly longer in p53-deficient mice compared with wild-type animals. Nevertheless, neuronal death in the hippocampal CA3 subfield and the neocortex was significantly reduced at 72 h in p53-deficient mice. Long-term continuous EEG telemetry recordings after status epilepticus determined that the sum duration of spontaneous seizures was significantly longer in p53-deficient compared with wild-type mice. Hippocampal damage and neuropeptide Y distribution at the end of chronic recordings was found to be similar between p53-deficient and wild-type mice. The present study identifies protracted KA-induced electrographic status as a novel outcome of p53 deficiency and shows that the absence of p53 leads to an exacerbated epileptic phenotype. Accordingly, targeting p53 to protect against status epilepticus or related neurologic insults may be offset by deleterious consequences of reduced p53 function during epileptogenesis or in chronic epilepsy