Delivery of Alkaline Phosphatase Promotes Periodontal Regeneration in Mice.

Factors regulating the ratio of pyrophosphate (PPi) to phosphate (Pi) modulate biomineralization. Tissue-nonspecific alkaline phosphatase (TNAP) is a key promineralization enzyme that hydrolyzes the potent mineralization inhibitor PPi. The goal of this study was to determine whether TNAP could promote periodontal regeneration in bone sialoprotein knockout mice (Ibsp-/- mice), which are known to have a periodontal disease phenotype. Delivery of TNAP was accomplished either systemically (through a lentiviral construct expressing a mineral-targeted TNAP-D10 protein) or locally (through addition of recombinant human TNAP to a fenestration defect model). Systemic TNAP-D10 delivered by intramuscular injection at 5 d postnatal (dpn) increased circulating alkaline phosphatase (ALP) levels in Ibsp-/- mice by 5-fold at 30 dpn, with levels returning to normal by 60 dpn when tissues were evaluated by micro-computed tomography and histology. Local delivery of recombinant human TNAP to fenestration defects in 5-wk-old wild type (WT) and Ibsp-/- mice did not alter long-term circulating ALP levels, and tissues were evaluated by micro-computed tomography and histology at postoperative day 45. Systemic and local delivery of TNAP significantly increased alveolar bone volume (20% and 37%, respectively) and cementum thickness (3- and 42-fold) in Ibsp-/- mice, with evidence for periodontal ligament attachment and bone/cementum marker localization. Local delivery significantly increased regenerated cementum and bone in WT mice. Addition of 100-µg/mL bovine intestinal ALP to culture media to increase ALP in vitro increased media Pi concentration, mineralization, and Spp1 and Dmp1 marker gene expression in WT and Ibsp-/- OCCM.30 cementoblasts. Use of phosphonoformic acid, a nonspecific inhibitor of sodium Pi cotransport, indicated that effects of bovine intestinal ALP on mineralization and marker gene expression were in part through Pi transport. These findings show for the first time through multiple in vivo and in vitro approaches that pharmacologic modulation of Pi/PPi metabolism can overcome periodontal breakdown and accomplish regeneration.

Ablation of Pyrophosphate Regulators Promotes Periodontal Regeneration.

Biomineralization is regulated by inorganic pyrophosphate (PPi), a potent physiological inhibitor of hydroxyapatite crystal growth. Progressive ankylosis protein (ANK) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) act to increase local extracellular levels of PPi, inhibiting mineralization. The periodontal complex includes 2 mineralized tissues, cementum and alveolar bone (AB), both essential for tooth attachment. Previous studies demonstrated that loss of function of ANK or ENPP1 (reducing PPi) resulted in increased cementum formation, suggesting PPi metabolism may be a target for periodontal regenerative therapies. To compare the effects of genetic ablation of Ank, Enpp1, and both factors concurrently on cementum and AB regeneration, mandibular fenestration defects were created in Ank knockout (Ank KO), Enpp1 mutant (Enpp1asj/asj), and double KO (dKO) mice. Genetic ablation of Ank, Enpp1, or both factors increased cementum regeneration compared to controls at postoperative days (PODs) 15 and 30 (Ank KO: 8-fold, 3-fold; Enpp1asj/asj: 7-fold, 3-fold; dKO: 11-fold, 4-fold, respectively) associated with increased fluorochrome labeling and expression of mineralized tissue markers, dentin matrix protein 1 (Dmp1/DMP1), osteopontin (Spp1/OPN), and bone sialoprotein (Ibsp/BSP). Furthermore, dKO mice featured increased cementum thickness compared to single KOs at POD15 and Ank KO at POD30. No differences were noted in AB volume between genotypes, but osteoblast/osteocyte markers were increased in all KOs, partially mineralized osteoid volume was increased in dKO versus controls at POD15 (3-fold), and mineral density was decreased in Enpp1asj/asj and dKOs at POD30 (6% and 9%, respectively). Increased numbers of osteoclasts were present in regenerated AB of all KOs versus controls. These preclinical studies suggest PPi modulation as a potential and novel approach for cementum regeneration, particularly targeting ENPP1 and/or ANK. Differences in cementum and AB regeneration in response to reduced PPi conditions highlight the need to consider tissue-specific responses in strategies targeting regeneration of the entire periodontal complex.

Influence of particulate matter on human health in selected African provinces: mini-review.

Air contamination influenced the human health and environmental well-being of the ecosystem. Particulate matter is a series of issues from major air pollutants in atmosphere. The aim of the review was to analyses the influence of particulate matter on human health and estimate the number of populations exposed to air pollution. The data analysed using the Environmental Benefits Mapping Analysis program model to selected African provinces. The review used 15% rollback data from the global burden disease and 5.8 µg/m³ the concentration of air pollutants from 1990 to 2013 years. The main findings of the study revealed that about 370 million (36.6%) population affected by air pollution. Besides, the risk factor associated with a population was 53,000 deaths per total population and 50,000 life-year losses. The economic value estimated to avoid a single case of particular matter on human health effect were estimated 14 billion dollars (US 2011). Priorities should be given to air quality management to improve the human and environmental health of ecosystems to reduce the global burden of disease of Africa regions.

Least concern to endangered: Applying climate change projections profoundly influences the extinction risk assessment for wild Arabica coffee.

Arabica coffee (Coffea arabica) is a key crop in many tropical countries and globally provides an export value of over US$13 billion per year. Wild Arabica coffee is of fundamental importance for the global coffee sector and of direct importance within Ethiopia, as a source of harvestable income and planting stock. Published studies show that climate change is projected to have a substantial negative influence on the current suitable growing areas for indigenous Arabica in Ethiopia and South Sudan. Here we use all available future projections for the species based on multiple general circulation models (GCMs), emission scenarios, and migration scenarios, to predict changes in Extent of Occurrence (EOO), Area of Occupancy (AOO), and population numbers for wild Arabica coffee. Under climate change our results show that population numbers could reduce by 50% or more (with a few models showing over 80%) by 2088. EOO and AOO are projected to decline by around 30% in many cases. Furthermore, present-day models compared to the near future (2038), show a reduction for EOO of over 40% (with a few cases over 50%), although EOO should be treated with caution due to its sensitivity to outlying occurrences. When applying these metrics to extinction risk, we show that the determination of generation length is critical. When applying the International Union for Conservation of Nature's Red list of Threatened Species (IUCN Red List) criteria, even with a very conservative generation length of 21 years, wild Arabica coffee is assessed as Threatened with extinction (placed in the Endangered category) under a broad range of climate change projections, if no interventions are made. Importantly, if we do not include climate change in our assessment, Arabica coffee is assessed as Least Concern (not threatened) when applying the IUCN Red List criteria.

A Combination of Surgery and Methotrexate for Successful Treatment of a Caesarean Scar Pregnancy.

Caesarean scar ectopic pregnancy (CSEP) is one of the rarest forms of ectopic pregnancies. With rising caesarean delivery (CD) rates worldwide, there is an increase in the incidence of CSEP. Patients usually present with painless vaginal bleeding and often misdiagnosed as spontaneous miscarriage. The use of ultrasonography with colour flow Doppler helps in the differential diagnosis. Different treatment options are described in the literature, although there is insufficient evidence regarding the best approach. We report the diagnosis and management of a case of CSEP in a woman with four previous CD who presented with vaginal bleeding and lower abdominal cramps at six weeks of gestation. She was treated with laparoscopic and ultrasound guided aspiration of the gestational sac and local injection of methotrexate supplemented by intramuscular methotrexate injection.

Resilience potential of the Ethiopian coffee sector under climate change.

Coffee farming provides livelihoods for around 15 million farmers in Ethiopia and generates a quarter of the country's export earnings. Against a backdrop of rapidly increasing temperatures and decreasing rainfall, there is an urgent need to understand the influence of climate change on coffee production. Using a modelling approach in combination with remote sensing, supported by rigorous ground-truthing, we project changes in suitability for coffee farming under various climate change scenarios, specifically by assessing the exposure of coffee farming to future climatic shifts. We show that 39-59% of the current growing area could experience climatic changes that are large enough to render them unsuitable for coffee farming, in the absence of significant interventions or major influencing factors. Conversely, relocation of coffee areas, in combination with forest conservation or re-establishment, could see at least a fourfold (>400%) increase in suitable coffee farming area. We identify key coffee-growing areas that are susceptible to climate change, as well as those that are climatically resilient.

QTL mapping identifies a major locus for resistance in wheat to Sunn pest (Eurygaster integriceps) feeding at the vegetative growth stage.

KEY MESSAGE: This research provides the first report of a major locus controlling wheat resistance to Sunn pest. It developed and validated SNP markers that will be useful for marker-assisted selection. Sunn pest (Eurygaster integriceps Puton) is the most destructive insect pest of bread wheat and durum wheat in West and Central Asia and East Europe. Breeding for resistance at the vegetative stage of growth is vital in reducing the damage caused by overwintered adult populations that feed on shoot and leaves of seedlings, and in reducing the next generation of pest populations (nymphs and adults), which can cause damage to grain quality by feeding on spikes. In the present study, two doubled haploid (DH) populations involving resistant landraces from Afghanistan were genotyped with the 90k SNP iSelect assay and candidate gene-based KASP markers. The DH lines and parents were phenotyped for resistance to Sunn pest feeding, using artificial infestation cages at Terbol station, in Lebanon, over three years. Quantitative trait locus (QTL) analysis identified a single major locus on chromosome 4BS in the two populations, with the resistance allele derived from the landrace accessions, IG139431 and IG139883. The QTL explained a maximum of 42 % of the phenotypic variation in the Cham6 × IG139431 and 56 % in the Cham6 × IG139883 populations. SNP markers closest to the QTL showed high similarity to rice genes that putatively encode proteins for defense response to herbivory and wounding. The markers were validated in a large, unrelated population of parental wheat genotypes. All wheat lines carrying the 'C-G' haplotype at the identified SNPs were resistant, suggesting that selection based on a haplotype of favourable alleles would be effective in predicting resistance status of unknown genotypes.

Genome-Wide Association Mapping of Yield and Grain Quality Traits in Winter Wheat Genotypes.

The main goal of this study was to investigate the genetic basis of yield and grain quality traits in winter wheat genotypes using association mapping approach, and identify linked molecular markers for marker assisted selection. A total of 120 elite facultative/winter wheat genotypes were evaluated for yield, quality and other agronomic traits under rain-fed and irrigated conditions for two years (2011-2012) at the Tel Hadya station of ICARDA, Syria. The same genotypes were genotyped using 3,051 Diversity Array Technologies (DArT) markers, of which 1,586 were of known chromosome positions. The grain yield performance of the genotypes was highly significant both in rain-fed and irrigated sites. Average yield of the genotypes ranged from 2295 to 4038 kg/ha and 4268 to 7102 kg/ha under rain-fed and irrigated conditions, respectively. Protein content and alveograph strength (W) ranged from 13.6-16.1% and 217.6-375 Jx10-4, respectively. DArT markers wPt731910 (3B), wPt4680 (4A), wPt3509 (5A), wPt8183 (6B), and wPt0298 (2D) were significantly associated with yield under rain-fed conditions. Under irrigated condition, tPt4125 on chromosome 2B was significantly associated with yield explaining about 13% of the variation. Markers wPt2607 and wPt1482 on 5B were highly associated with protein content and alveograph strength explaining 16 and 14% of the variations, respectively. The elite genotypes have been distributed to many countries using ICARDA's International system for potential direct release and/or use as parents after local adaptation trials by the NARSs of respective countries. The QTLs identified in this study are recommended to be used for marker assisted selection after through validation using bi-parental populations.

Peripartum hysterectomy in the first decade of the 21st century.

We reviewed the role of peripartum hysterectomy (PH) in the first decade of the 21st century. The study was confined to women who delivered a baby weighing 500 g or more between 2000 and 2009, and who required a hysterectomy within 72 h of delivery for obstetric reasons. Individual case records were reviewed. There were 19 cases of PH in 78,961 deliveries giving an incidence of 1 in 4,156 (0.02%). Of the 19 cases, 95% were delivered by caesarean section and 89% had one or more prior sections. The indications were placental bed pathology (79%), uterine atony (16%) and uterine trauma (5%). Of the 19 hysterectomies, 16 (84%) were total and a gynaecological oncologist was involved in nine (56%) of these cases. There were no maternal or fetal deaths, but a mother required an average blood transfusion of 10 units. The overall rate of PH was remarkably low compared with other studies but it is likely to increase in the future because of the strong association between increasing caesarean section rates and placental bed pathology. The potential involvement of the cervix and other pelvic structures by placental pathology means that PH in the future will be more challenging, and the hysterectomy will need to be total rather than subtotal.

Chromosomal location and molecular mapping of a tan spot resistance gene in the winter wheat cultivar Red Chief.

The winter wheat cultivar Red Chief has been identified as the wheat cultivar most resistant to Pyrenophora tritici-repentis (Ptr). This study was undertaken to determine the inheritance, chromosomal location and molecular mapping of a tan spot resistance gene in Red Chief. χ² analysis of the F2 segregation data of the hybrids between 21 monosomic lines of the susceptible wheat cultivar Chinese Spring and the resistant cultivar Red Chief revealed that tan spot resistance in cv. Red Chief is controlled by a single recessive gene located on chromosome 3A. Linkage analysis using SSR markers in the Red Chief/Chinese Spring F2 population showed that the tsr4 gene is clustered in the region around Xgwm2a, on the short arm of chromosome 3A. This marker has also been identified as the closest marker to the tsr3 locus on chromosome 3D in synthetic wheat lines. Validation analysis of this marker for the tsr3 and tsr4 genes using 28 resistant and 6 susceptible genotypes indicated that the 120 bp allele (the tsr3 gene) specific fragment was observed in 11 resistant genotypes, including the three synthetic lines XX41, XX45 and XX110, while the 130 bp allele was amplified only in cv. Red Chief and Dashen. Xgwm2a can be used to trace the presence of the target gene in successive backcross generations and pyramiding of the tsr3 & tsr4 genes into a commonly grown and adaptable cultivar.

Molecular mapping of resistance genes to tan spot [Pyrenophora tritici-repentis race 1] in synthetic wheat lines.

Synthetic wheat lines (2n = 6x = 42, AABBDD), which are amphiploids developed from the hybrid between tetraploid wheat (Triticum turgidum L., 2n = 4x = 28, AABB) and Aegilops tauschii Coss. (2n = 2x = 14, DD), are important sources of resistance against tan spot of wheat caused by Pyrenophora tritici-repentis. In the present study, inheritance, allelism and genetic linkage analysis in synthetic wheat lines have been carried out. Segregation analysis of the phenotypic and molecular data in F(2:3) populations of CS/XX41, CS/XX45, and CS/XX110 has revealed a 1:2:1 segregation ratio indicating that resistance of tan spot in these synthetic lines is controlled by a single gene. Allelism tests detected no segregation for susceptibility among F(1) and F(2) plants derived from intercrosses of the resistance lines XX41, XX45 and XX110 indicating that the genes are either allelic or tightly linked. Linkage analysis using SSR markers showed that all the three genes: tsn3a in XX41, Tsn3b in XX45 and tsn3c in XX110 are clustered in the region around Xgwm2a, located on the short arm of chromosome 3D. The linked markers and genetic relationship of these genes will greatly facilitate their use in wheat breeding and deployment of cultivars resistant to tan spot.

HIV/AIDS in Ethiopia: where is the epidemic heading?

OBJECTIVES: A possible decline in prevalence of HIV in some sub-Saharan African countries has been reported recently. The present study aimed to evaluate the prevalence and incidence of HIV and behavioural data to investigate trends in HIV/AIDS in Ethiopia. METHODS: A review was conducted of published reports and literature, raw and modelled (using Epidemic Projection Package and Spectrum software) surveillance data and estimates from antenatal clinics (ANCs) and data from voluntary counselling and testing centres. Observations were restricted to the adult population. RESULTS: Between 2001 and 2003, more ANC sites showed a decline than a rise in HIV prevalence, but most lacked statistical significance. Modelled data suggested a rise in prevalence of HIV in rural areas (2003: 2.6%) and in all Ethiopia (2003: 4.4%), but a stable or declining prevalence in Addis Ababa (2003: 14.6%) and other urban areas (2003: 11.8%). Modelled HIV incidence, inferred from prevalence changes, showed a slowly rising trend in Addis Ababa (2003: 2.0%), other urban areas (2003: 1.7%), and rural Ethiopia (2003: 0.46%). The total burden of HIV/AIDS is expected also to rise substantially due to population growth. In Addis Ababa, crude data on HIV prevalence from ANCs too suggested a falling trend. Voluntary counselling and testing data from 2002 to 2004 supported this trend but indicated a mixed trend pattern for high risk behaviour. No other serial behavioural trend data were available. CONCLUSIONS: Lack of quality data on behavioural trends impedes the interpretation of prevalence and incidence data in Ethiopia. Modelled data suggest an expanding HIV epidemic in rural and all Ethiopia, but a possible decline in some urban areas. Crude site prevalence values may be more sensitive to acute changes, possibly indicating a slowing/reversal of the epidemic's expansion.

The isolation of salmonellae from poultry carcasses and equipment in the poultry processing plant by means of two procedures.

A total of 235 samples (swabs, rinse and organs) from freshly dressed broiler carcasses and from equipment of poultry processing plant were examined for the presence of salmonellae by means of motility enrichment on modified semisolid Rappaport medium (SAM) and of a conventional cultural procedure using Rappaport-Vassiliadis broth (R-VB) as selective enrichment. In 61 samples (26%), Salmonella was isolated by means of one or both procedures. The highest contamination with Salmonella was found in the rinse of broiler carcasses (35.5%), followed by swabs of equipment (32.0%), tissues of organs (31.0%) and swabs of carcasses (19.7%). Twelve different serotypes and 65 strains of salmonellae were detected. S. saint paul and S. enteritidis were the most frequent serotypes. Statistical analysis showed that there was no significant difference between the procedures.