Genomic features of human limb specific enhancers.

To elucidate important cellular and molecular interactions that regulate patterning and skeletal development, vertebrate limbs served as a model organ. A growing body of evidence from detailed studies on a subset of limb regulators like the HOXD cluster or SHH, reveals the importance of enhancers in limb related developmental and disease processes. Exploiting the recent genome-wide availability of functionally confirmed enhancer dataset, this study establishes regulatory interactions for dozens of human limb developmental genes. From these data, it appears that the long-range regulatory interactions are fairly common during limb development. This observation highlights the significance of chromosomal breaks/translocations in human limb deformities. Transcriptional factor (TF) analysis predicts that the differentiation of early nascent limb-bud into future territories entail distinct TF interaction networks. Conclusively, an important motivation for annotating the human limb specific regulatory networks is to pave way for the systematic exploration of their role in disease and evolution.

ATLANTIS - Attractor Landscape Analysis Toolbox for Cell Fate Discovery and Reprogramming.

Boolean modelling of biological networks is a well-established technique for abstracting dynamical biomolecular regulation in cells. Specifically, decoding linkages between salient regulatory network states and corresponding cell fate outcomes can help uncover pathological foundations of diseases such as cancer. Attractor landscape analysis is one such methodology which converts complex network behavior into a landscape of network states wherein each state is represented by propensity of its occurrence. Towards undertaking attractor landscape analysis of Boolean networks, we propose an Attractor Landscape Analysis Toolbox (ATLANTIS) for cell fate discovery, from biomolecular networks, and reprogramming upon network perturbation. ATLANTIS can be employed to perform both deterministic and probabilistic analyses. It has been validated by successfully reconstructing attractor landscapes from several published case studies followed by reprogramming of cell fates upon therapeutic treatment of network. Additionally, the biomolecular network of HCT-116 colorectal cancer cell line has been screened for therapeutic evaluation of drug-targets. Our results show agreement between therapeutic efficacies reported by ATLANTIS and the published literature. These case studies sufficiently highlight the in silico cell fate prediction and therapeutic screening potential of the toolbox. Lastly, ATLANTIS can also help guide single or combinatorial therapy responses towards reprogramming biomolecular networks to recover cell fates.

Effects of the hydro-ethanolic extract of Marrubium vulgare in female rats

OBJECTIVE@#To evaluate the effects of ethanol-water (80:20) extract of Marrubium vulgare (M. vulgare) on the hematological parameters, macroscopic and histological aspects of the uterus and fetus in non-pregnant and pregnant rats.@*METHODS@#Female rats were divided into 4 equal groups (n = 9), group N (normal rats) and group G (pregnant rats) considered as control groups, group NE (normal rats treated with the ethanol-water (80:20, v/v) extract of M. vulgare) and group GE (pregnant rats treated with the extract). The ethanol-water (80:20) plant extract was administered in a single daily dose 1 g/kg at the morning, during 19 d. On the 19 day of the experiment, animals were sacrificed, the uterus and fetuses were removed for the morphological and histological studies and the blood was collected in EDTA tubes for the measurement of hematological parameters with the use of an automate 'HORIBA ABX Micros 60 Hematology Analyzer'.@*RESULTS@#Our results showed, in group NE and GE, a significant decrease on hematological parameters: red blood cells (NE: 18.6%; GE: 38.4%), hematocrit (NE: 13.8%; GE: 20.4%), hemoglobin (NE: 12.1%; GE: 8.3%) and mean corpuscular volume (NE: 6.4%; GE: 2%) with P more less a 0.05. Indeed, the extract of M. vulgare caused a significant decrease on the mean implantations of fetuses (82.5%, P < 0.001) and their size (47.2%, P < 0.01). As for the macroscopic and histological appearance of uterus, our data showed no change in normal treated rats. In contrast, the treated pregnant rats showed a severe histological change characterized by the existence of location of stopped gestation. Furthermore, it was also found in the uterus of these rat lyses placental and embryo tissue.@*CONCLUSIONS@#All these results support the hypothesis of an abortifacient effect of M. vulgare.

A lower-cost protocol for sickle cell disease neonatal screening in Tunisia.

BACKGROUND AND OBJECTIVES: Sickle cell disease (SCD) is a group of hereditary chronic anemias that manifest essentially as painful crisis and susceptibility to infection. Neonatal screening is a preventive action that reduces the rates of mortality due to complications arising from infections by encouraging early prophylactic penicillin use and pneumococcal vaccination. The purpose of this pilot study was to set up a neonatal screening protocol at a lower cost than one that uses commercially available screening kits. DESIGN AND SETTING: Pilot study conducted over 1 year in two Tunis maternity hospitals. PATIENTS AND METHODS: Samples from 9148 newborns were collected using paper printed using a common office printer to collect blood spots from the newborns. A lab-prepared agarose gel for isoelectrofocusing (IEF) was used to test the dried blood samples from these newborns. RESULTS: The IEF on lab-prepared agarose gels was efficient since it was able to detect the main abnormal Hbs previously identified in the Tunisian population (HbS, HbC, HbO, and HbG). Furthermore, when data collected in this screening program were compared with the previously established national data, no statistically significant differences were found. After analysis, results were given back to the families of the patients, and the major Hb cases were directed to one of the hemoglobinopathies specialized centers, where at-risk couples benefited from genetic counselling and were informed about the possibility of prenatal diagnosis. CONCLUSION: This pilot experiment demonstrated the feasibility of SCD neonatal detection using a lower cost method as well as detection of other main structural Hb variants.

Effects of the hydro-ethanolic extract of Marrubium vulgare in female rats

Objective To evaluate the effects of ethanol–water (80:20) extract of Marrubium vulgare (M. vulgare) on the hematological parameters, macroscopic and histological aspects of the uterus and fetus in non-pregnant and pregnant rats. Methods Female rats were divided into 4 equal groups (n = 9), group N (normal rats) and group G (pregnant rats) considered as control groups, group NE (normal rats treated with the ethanol–water (80:20, v/v) extract of M. vulgare) and group GE (pregnant rats treated with the extract). The ethanol–water (80:20) plant extract was administered in a single daily dose 1 g/kg at the morning, during 19 d. On the 19 day of the experiment, animals were sacrificed, the uterus and fetuses were removed for the morphological and histological studies and the blood was collected in EDTA tubes for the measurement of hematological parameters with the use of an automate ‘HORIBA ABX Micros 60 Hematology Analyzer’. Results Our results showed, in group NE and GE, a significant decrease on hematological parameters: red blood cells (NE: 18.6%; GE: 38.4%), hematocrit (NE: 13.8%; GE: 20.4%), hemoglobin (NE: 12.1%; GE: 8.3%) and mean corpuscular volume (NE: 6.4%; GE: 2%) with P more less a 0.05. Indeed, the extract of M. vulgare caused a significant decrease on the mean implantations of fetuses (82.5%, P < 0.001) and their size (47.2%, P < 0.01). As for the macroscopic and histological appearance of uterus, our data showed no change in normal treated rats. In contrast, the treated pregnant rats showed a severe histological change characterized by the existence of location of stopped gestation. Furthermore, it was also found in the uterus of these rat lyses placental and embryo tissue. Conclusions All these results support the hypothesis of an abortifacient effect of M. vulgare.