Fresh and in vitro osteodifferentiated human amniotic membrane,alone or associated with an additional scaffold,does not induce ectopic bone formation in Balb/c mice

The human amniotic membrane (hAM) has been successfully used as a natural carrier containing amniotic mesenchymal stromal cells, epithelial cells and growth factors. It has a little or no immunogenicity, and possesses useful anti-microbial, anti-inflammatory, anti-fibrotic and analgesic properties. It has been used for many years in several indications for soft tissue repair. We previously reported that hAM represents a natural and preformed sheet containing highly potent stem cells, and could thus be used for bone repair. Indeed, native hAM possesses pre-osteoblastic potential that can easily be stimulated, even as far as mineralization, by means of in vitro osteogenic culture. However, cell culture induces damage to the tissue, as well as to cell phenotype and function. The aim of this study was to evaluate new bone formation by fresh and in vitro osteodifferentiated hAM, alone or associated with an additional scaffold presenting osteoinductive properties. Moreover, we also aimed to determine the effect of in vitro hAM pre-osteodifferentiation on its in vivo biocompatibility/tissue degradation. Results showed that neither fresh nor osteodifferentiated hAM induced ectopic bone formation, whether or not it was associated with the osteoinductive scaffold. Secondly, fresh and osteodifferentiated hAM presented similar in vivo tissue degradation, suggesting that in vitro hAM pre-osteodifferentiation did not influence its in vivo biocompatibility.     

The ‘Checkmate’ for Iron Between Human Host and Invading Bacteria: Chess Game Analogy

Iron is an essential nutrient for all living organisms with critical roles in many biological processes. The mammalian host maintains the iron requirements by dietary intake, while the invading pathogenic bacteria compete with the host to obtain those absorbed irons. In order to limit the iron uptake by the bacteria, the human host employs numerous iron binding proteins and withholding defense mechanisms that capture iron from the microbial invaders. To counteract, the bacteria cope with the iron limitation imposed by the host by expressing various iron acquisition systems, allowing them to achieve effective iron homeostasis. The armamentarium used by the human host and invading bacteria, leads to the dilemma of who wins the ultimate war for iron.     

Somatosensory areas S2 and PV project to the superior colliculus of a prosimian primate, Galago garnetti

As part of an effort to describe the connections of the somatosensory system in Galago garnetti, a small prosimian primate, injections of tracers into cortex revealed that two somatosensory areas, the second somatosensory area (S2) and the parietal ventral somatosensory area (PV), project densely to the ipsilateral superior colliculus, while the primary somatosensory area (S1 or area 3b) does not. The three cortical areas were defined in microelectrode mapping experiments and recordings were used to identify appropriate injection sites in the same cases. Injections of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) were placed in S1 in different mediolateral locations representing body regions from toes to face in five galagos, and none of these injections labeled projections to the superior colliculus. In contrast, each of the two injections in the face representation of S2 in two galagos and three injections in face and forelimb representations of PV in three galagos produced dense patches of labeled terminations and axons in the intermediate gray (layer IV) over the full extent of the superior colliculus. The results suggest that the higher-order somatosensory areas, PV and S2, are directly involved in the visuomotor functions of the superior colliculus in prosimian primates, while S1 is not. The somatosensory inputs appear to be too widespread to contribute to a detailed somatotopic representation in the superior colliculus, but they may be a source of somatosensory modulation of retinotopically guided oculomotor instructions.     

Safety and Effectiveness of Combination Antiretroviral Therapy during the First Year of Treatment in HIV-1 Infected Rwandan Children: A Prospective Study

Background

With increased availability of paediatric combination antiretroviral therapy (cART) in resource limited settings, cART outcomes and factors associated with outcomes should be assessed.

Methods

HIV-infected children <15 years of age, initiating cART in Kigali, Rwanda, were followed for 18 months. Prospective clinical and laboratory assessments included weight-for-age (WAZ) and height-for-age (HAZ) z-scores, complete blood cell count, liver transaminases, creatinine and lipid profiles, CD4 T-cell count/percent, and plasma HIV-1 RNA concentration. Clinical success was defined as WAZ and WAZ >−2, immunological success as CD4 cells ≥500/mm³ and ≥25% for respectively children over 5 years and under 5 years, and virological success as a plasma HIV-1 RNA concentration <40 copies/mL.

Results

Between March 2008 and December 2009, 123 HIV-infected children were included. The median (interquartile (IQR) age at cART initiation was 7.4 (3.2, 11.5) years; 40% were <5 years and 54% were female. Mean (95% confidence interval (95%CI)) HAZ and WAZ at baseline were −2.01 (−2.23, −1.80) and −1.73 (−1.95, −1.50) respectively and rose to −1.75 (−1.98, −1.51) and −1.17 (−1.38, −0.96) after 12 months of cART. The median (IQR) CD4 T-cell values for children <5 and ≥5 years of age were 20% (13, 28) and 337 (236, 484) cells/mm³respectively, and increased to 36% (28, 41) and 620 (375, 880) cells/mm³. After 12 months of cART, 24% of children had a detectable viral load, including 16% with virological failure (HIV-RNA>1000 c/mL). Older age at cART initiation, poor adherence, and exposure to antiretrovirals around birth were associated with virological failure. A third (33%) of children had side effects (by self-report or clinical assessment), but only 9% experienced a severe side effect requiring a cART regimen change.

Conclusions

cART in Rwandan HIV-infected children was successful but success might be improved further by initiating cART as early as possible, optimizing adherence and optimizing management of side effects.     

Contrasted allometries between stem diameter,crown area,and tree height in five tropical biogeographic areas

Key message

Across five biogeographic areas, DBH-CA allometry was characterized by inter-site homogeneity and intra-site heterogeneity, whereas the reverse was observed for DBH-H allometry.

Abstract

Tree crowns play a central role in stand dynamics. Remotely sensed canopy images have been shown to allow inferring stand structure and biomass which suggests that allometric scaling between stems and crowns may be tight, although insufficiently investigated to date. Here, we report the first broad-scale assessment of stem vs. crown scaling exponents using measurements of bole diameter (DBH), total height (H), and crown area (CA) made on 4148 trees belonging to 538 species in five biogeographic areas across the wet tropics. Allometries were fitted with power functions using ordinary least-squares regressions on log-transformed data. The inter-site variability and intra-site (sub-canopy vs. canopy trees) variability of the allometries were evaluated by comparing the scaling exponents. Our results indicated that, in contrast to both DBH-H and H-CA allometries, DBH-CA allometry shows no significant inter-site variation. This fairly invariant scaling calls for increased effort in documenting crown sizes as part of tree morphology. Stability in DBH-CA allometry, indeed, suggests that some universal constraints are sufficiently pervasive to restrict the exponent variation to a narrow range. In addition, our results point to inverse changes in the scaling exponent of the DBH-CA vs. DBH-H allometries when shifting from sub-canopy to canopy trees, suggesting a change in carbon allocation when a tree reaches direct light. These results pave the way for further advances in our understanding of niche partitioning in tree species, tropical forest dynamics, and to estimate AGB in tropical forests from remotely sensed images.

     

Phylogenomic approaches reveal how climate shapes patterns of genetic diversity in an African rain forest tree species

The world's second largest expanse of tropical rainforest is in Central Africa, and it harbours enormous species diversity. Population genetic studies have consistently revealed significant structure across Central African rainforest plants. In particular, previous studies have repeatedly demonstrated a north–south genetic discontinuity around the equatorial line, in a continuous expanse of rainforest where a climatic inversion is documented. Here, we took a phylogeographic approach by sequencing 351 nuclear markers in 112 individuals across the distribution of the African rainforest tree species Annickia affinis (Annonaceae). We showed for the first time that the north–south divide is the result of a single, major colonization event across the climatic inversion from an ancestral population located in Gabon. We suggested that differences in ecological niche of populations located on either side of this inversion may have contributed to this phylogenetic discontinuity. We found evidence for inland dispersal, predominantly in northern areas, and variable demographic histories among genetic clusters, indicating that populations responded differently to past climate change. We show how newly developed genomic tools can provide invaluable insights into our understanding of tropical rainforest evolutionary dynamics.     

Expression and characterization of deletion recombinants of two cGMP-inhibited cyclic nucleotide phosphodiesterases (PDE-3)

cDNAs encoding two PDE-3 or cyclic GMP-inhibited (cGI) cyclic nucleotide phosphodiesterase (PDE) isoforms, RPDE-3B (RcGIP1) and HPDE-3A (HcGIP2), were cloned from rat (R) adipose tissue and human (H) heart cDNA libraries. Deletion and N- and C-terminal truncation mutants were expressed inEscherichia coli in order to define their catalytic core. Active mutants of both RPDE-3B and HPDE-3A included the domain conserved among all PDEs plus additional upstream and downstream sequences. An RPDE-3B mutant consisting of the conserved domain alone and one from which the RPDE-3B 44-amino acid insertion was deleted exhibited little or no activity. All active recombinants exhibited a high affinity (<1 μM) for cyclic AMP (cAMP) and cyclic GMP (cGMP), were inhibited by cAMP, cGMP, and cilostamide, but not by rolipram, and were photolabeled with [³²P]-cGMP. The IC₅₀ values for cGMP inhibition of cAMP hydrolysis were lower for HPDE-3A than for RPDE-3B recombinants. The deduced amino acid sequences of HPDE-3A and RPDE-3B catalytic domains are very similar except for the 44-amino acid insertion not found in other PDEs. It is possible that this insertion may not only distinguish PDE-3 catalytic domains from other PDEs and identify catalytic domains of PDE-3 subfamilies or conserved members of the PDE-3 gene family, but may also be involved in the regulation of sensitivity of PDE-3s to cGMP. These authors contributed equally to this work.     

Circulating Angiogenic Factors and the Risk of Adverse Outcomes among Haitian Women with Preeclampsia

ObjectiveAngiogenic factors are strongly associated with adverse maternal and fetal outcomes among women with preterm preeclampsia (PE) in developed countries. We evaluated the role of angiogenic factors and their relationship to adverse outcomes among Haitian women with PE.ResultsAmong patients with PE, most (24/35) were admitted at term. Adverse outcome rates in PE were much higher among the early onset group compared to the late onset group (100.0% vs. 54.2%, P=0.007). Plasma angiogenic factors were dramatically altered in both subtypes of PE. Angiogenic factors also correlated with adverse outcomes in both subtypes of PE. The median sFlt1/PlGF ratios for subjects with early onset PE with any adverse outcome vs. NHD <=34 weeks with no adverse outcome were 703.1 (146.6, 1614.9) and 9.6 (3.5, 58.6); P<0.001). Among late onset group the median sFlt1/PlGF ratio for women with any adverse outcome was 130.7 (56.1, 242.6) versus 22.4 (10.2, 58.7; P=0.005) in NHD >34 weeks with no adverse outcome.ConclusionPE-related adverse outcomes are common in women in Haiti and are associated with profound angiogenic imbalance regardless of gestational age at presentation.     

Somatosensory areas S2 and PV project to the superior colliculus of a prosimian primate,Galago garnetti

As part of an effort to describe the connections of the somatosensory system in Galago garnetti, a small prosimian primate, injections of tracers into cortex revealed that two somatosensory areas, the second somatosensory area (S2) and the parietal ventral somatosensory area (PV), project densely to the ipsilateral superior colliculus, while the primary somatosensory area (S1 or area 3b) does not. The three cortical areas were defined in microelectrode mapping experiments and recordings were used to identify appropriate injection sites in the same cases. Injections of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) were placed in S1 in different mediolateral locations representing body regions from toes to face in five galagos, and none of these injections labeled projections to the superior colliculus. In contrast, each of the two injections in the face representation of S2 in two galagos and three injections in face and forelimb representations of PV in three galagos produced dense patches of labeled terminations and axons in the intermediate gray (layer IV) over the full extent of the superior colliculus. The results suggest that the higher-order somatosensory areas, PV and S2, are directly involved in the visuomotor functions of the superior colliculus in prosimian primates, while S1 is not. The somatosensory inputs appear to be too widespread to contribute to a detailed somatotopic representation in the superior colliculus, but they may be a source of somatosensory modulation of retinotopically guided oculomotor instructions.