Caspase-14 but not caspase-3 is processed during the development of fetal mouse epidermis

The activation of caspases is a central step in apoptosis and may also be critical for terminal differentiation of epidermal keratinocytes (KC). In particular, caspase-3 has been implicated in the differentiation of embryonic KC as well as in programmed cell death of KC, and caspase-14 has been suggested to function in the formation or homeostasis of the stratum corneum (SC). To test the putative roles of these proteases, we determined their expression level and activation status during development of fetal mouse epidermis. The level of procaspase-3 did not change significantly during epidermal development, and enzyme activation was undetectable at any timepoint investigated. Despite the lack of active caspase-3, the newly formed stratum granulosum and the regressing periderm contained cells positive in the terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling assay, indicating that nuclear DNA was degraded without activation of caspase-3, thereby arguing against a proteolytic function of caspase-3 in embryonic KC differentiation. By contrast, caspase-14 increased in abundance from embryonic day 14.5 (E14.5) onwards and consistently localized to the suprabasal layers of fetal epidermis. The caspase-14 pro-enzyme was processed into its catalytic subunits, a step required for enzyme activity, on day E17.5, coinciding with SC formation. Thus, processing of procaspase-14 is not confined to air-exposed mature skin but also occurs during epidermal development in utero. In summary, this study demonstrates that caspase-14, but not caspase-3 activation coincides temporally and spatially with embryonic KC differentiation, suggesting a role for caspase-14 in terminally differentiated KC.     

Scaling Up Family Planning to Reduce Maternal and Child Mortality: The Potential Costs and Benefits of Modern Contraceptive Use in South Africa

Introduction

Family planning contributes significantly to the prevention of maternal and child mortality. However, many women still do not use modern contraception and the numbers of unintended pregnancies, abortions and subsequent deaths are high. In this paper, we estimate the service delivery costs of scaling up modern contraception, and the potential impact on maternal, newborn and child survival in South Africa.

Methods

The Family Planning model in Spectrum was used to project the impact of modern contraception on pregnancies, abortions and births in South Africa (2015-2030). The contraceptive prevalence rate (CPR) was increased annually by 0.68 percentage points. The Lives Saved Tool was used to estimate maternal and child deaths, with coverage of essential maternal and child health interventions increasing by 5% annually. A scenario analysis was done to test impacts when: the change in CPR was 0.1% annually; and intervention coverage increased linearly to 99% in 2030.

Results

If CPR increased by 0.68% annually, the number of pregnancies would reduce from 1.3 million in 2014 to one million in 2030. Unintended pregnancies, abortions and births decrease by approximately 20%. Family planning can avert approximately 7,000 newborn and child and 600 maternal deaths. The total annual costs of providing modern contraception in 2030 are estimated to be US$33 million and the cost per user of modern contraception is US$7 per year. The incremental cost per life year gained is US$40 for children and US$1,000 for mothers.

Conclusion

Maternal and child mortality remain high in South Africa, and scaling up family planning together with optimal maternal, newborn and child care is crucial. A huge impact can be made on maternal and child mortality, with a minimal investment per user of modern contraception.     

Environmental and dispersal controls of an annual plant’s distribution: how similar are patterns and apparent processes at two spatial scales?

At scales from microsites to entire ranges, species’ distributions reflect limited adaptation and/or limited dispersal. To what extent are specific distribution patterns and processes similar across scales? We investigated environmental effects—presumed because of adaptation—and independent spatial effects—presumed because of dispersal—on distribution at two scales (landscape patches of approximately 1,300 m², sampled along transects, and 4-m² cells, sampled in contiguous grids within populations) and on individual performance (water status, reproduction) in the California annual, Clarkia xantiana ssp. xantiana. Because water limitation helps set this species’ regional borders, we expected occupancy and performance at smaller scales to correlate with topographic and soil features affecting water relations. At the patch scale, environmental features associated with reduced water stress (i.e., steep slopes that face north; coarse, soft soils; igneous rather than metasedimentary parent rock) predicted occupancy. Spatial aggregation was not detected, but incomplete occupancy of apparently suitable patches indicated that dispersal limits occupancy. At the scale of small cells, relationships between environmental variables, occupancy, density, and performance varied among populations. Associations sometimes resembled those at the patch scale but sometimes opposed them. Spatial aggregation in cell occupancy and/or density occurred in all populations, implying limited dispersal, whereas spatial aggregation of water potential values in some populations might have arisen from spatially structured unmeasured environmental variables. Limited adaptation to drought and limited patch colonization appear to affect patch occupancy in C. xantiana ssp. xantiana, whereas smaller-scale patterns indicate consistent effects of limited dispersal and somewhat variable environmental effects.     

DNase 2 is the main DNA-degrading enzyme of the stratum corneum

The cornified layer, the stratum corneum, of the epidermis is an efficient barrier to the passage of genetic material, i.e. nucleic acids. It contains enzymes that degrade RNA and DNA which originate from either the living part of the epidermis or from infectious agents of the environment. However, the molecular identities of these nucleases are only incompletely known at present. Here we performed biochemical and genetic experiments to determine the main DNase activity of the stratum corneum. DNA degradation assays and zymographic analyses identified the acid endonucleases L-DNase II, which is derived from serpinB1, and DNase 2 as candidate DNases of the cornified layer of the epidermis. siRNA-mediated knockdown of serpinB1 in human in vitro skin models and the investigation of mice deficient in serpinB1a demonstrated that serpinB1-derived L-DNase II is dispensable for epidermal DNase activity. By contrast, knockdown of DNase 2, also known as DNase 2a, reduced DNase activity in human in vitro skin models. Moreover, the genetic ablation of DNase 2a in the mouse was associated with the lack of acid DNase activity in the stratum corneum in vivo. The degradation of endogenous DNA in the course of cornification of keratinocytes was not impaired by the absence of DNase 2. Taken together, these data identify DNase 2 as the predominant DNase on the mammalian skin surface and indicate that its activity is primarily targeted to exogenous DNA.     

The geography of demography: long-term demographic studies and species distribution models reveal a species border limited by adaptation

Potential causes of species' geographic distribution limits fall into two broad classes: (1) limited adaptation across spatially variable environments and (2) limited opportunities to colonize unoccupied areas. Combining demographic studies, analyses of demographic responses to environmental variation, and species distribution models, we investigated the causes of range limits in a model system, the eastern border of the California annual plant Clarkia xantiana ssp. xantiana. Vital rates of 20 populations varied with growing season temperature and precipitation: fruit number and overwinter survival of 1-year-old seeds declined steeply, while current-year seed germination increased modestly along west-to-east gradients in decreasing temperature, decreasing mean precipitation, and increasing variation in precipitation. Long-term stochastic finite rate of increase, λ(s), exhibited a fourfold range and varied among geologic surface materials as well as with temperature and precipitation. Growth rate declined significantly toward the eastern border, falling below 1 in three of the five easternmost populations. Distribution models employing demographically important environmental variables predicted low habitat favorability beyond the eastern border. Models that filtered or weighted population presences by λ(s) predicted steeper eastward declines in favorability and assigned greater roles in setting the distribution to among-year variation in precipitation and to geologic surface material. These analyses reveal a species border likely set by limited adaptation to declining environmental quality.     

Neogene stratigraphy of the Eastern basin,Samos island,Greece

Revision of the stratigraphy and depositional environmentsin the Eastern Neogene basin of Samos. Mapping, structural analysis together with new K/Ar dates provide the following general pattern: two fluvial-lacustrine cycles separated by a disconformity. Basal cycle is Astaracian-Vallesian, the disconformity occured between 9 and 8.5 MY, upper cycle is Turolian and has yielded the famous «Samos mammal fauna wich is between 8.5 and 7.0 MY old.