Bulgarian Bone Marrow Donors Registry—past and future directions

Recently Bulgarian Bone Marrow Donors Registry (BBMDR) has been established and since August 2005 it has been a member of Bone Marrow Donors Worldwide. Currently the number of healthy donors included in the BBMDR is relatively low. All donors included in the BBMDR are typed for HLA-A, -B, -DRB loci. Phylogenetic analysis based on HLA allele frequencies shows that Bulgarians were characterized with closest genetic similarity to Macedonians, Greeks, Romanians, Cretans and Sardinians in comparison to the other European and Mediterranean populations. On the contrary the second largest ethnic minority–the Roma were the closest to the other Roma populations and North Indians. These differences were due to the predominance of alleles and haplotypes that are specific for the Asian and the other Roma populations. These specific genetic profiles in the Bulgarian ethnic minorities justify the need of an adequate representation of minorities in BBMDR. Future directions for BBMDR development are discussed, including an increase of the total number of donors and these for ethnic minorities, as well the enhancement of the level of resolution of the HLA typing for the donors in the registry.     

Hormones and root-shoot relationships in flooded plants — an analysis of methods and results

Two aspects of root to shoot communication in flooded plants are discussed (i) the formation of porous aerenchyma that enhances the passage of oxygen, and other gases, from shoots to roots and (ii) the movement of the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) from roots to shoots in the transpiration stream, and the effect of this on ethylene production and epinastic curvature in the shoots. For aerenchyma studies a highly sensitive photoacoustic laser detector for ethylene was used to avoid interference associated with other methods of ethylene measurement that require tissue excision. ACC concentrations in xylem sap were measured by physico-chemical means to ensure correct identification and account for processing losses. Solute concentrations, e.g., abscisic acid (ABA), in xylem sap are shown to be distorted by temporary contamination caused by the method used to collect sap. Concentrations of solutes in xylem sap (e.g., ACC) are also altered by changes in sap flow brought about by conventional methods of sap collection or by experimental treatments such as flooding the soil. Ways of for overcoming these problems are described together with a summary of preliminary results.     

Foreword to the special issue entitled “Progress and future directions in soft tissue mechanics” in the Journal Biomechanics and Modeling in Mechanobiology

Biomechanics and Modeling in Mechanobiology -     

Modeling oscillatory control in NF-κB, p53 and Wnt signaling

Oscillations are commonly observed in cellular behavior and span a wide range of timescales, from seconds in calcium signaling to 24 hours in circadian rhythms. In between lie oscillations with time periods of 1-5 hours seen in NF-κB, p53 and Wnt signaling, which play key roles in the immune system, cell growth/death and embryo development, respectively. In the first part of this article, we provide a brief overview of simple deterministic models of oscillations. In particular, we explain the mechanism of saturated degradation that has been used to model oscillations in the NF-κB, p53 and Wnt systems. The second part deals with the potential physiological role of oscillations. We use the simple models described earlier to explore whether oscillatory signals can encode more information than steady-state signals. We then discuss a few simple genetic circuits that could decode information stored in the average, amplitude or frequency of oscillations. The presence of frequency-detector circuit downstream of NF-κB or p53 would be a strong clue that oscillations are important for the physiological response of these signaling systems.     

Recurrent Implantation Failure-update overview on etiology,diagnosis, treatment and future directions

Recurrent implantation failure (RIF) refers to cases in which women have had three failed in vitro fertilization (IVF) attempts with good quality embryos. The definition should also take advanced maternal age and embryo stage into consideration. The failure of embryo implantation can be a consequence of uterine, male, or embryo factors, or the specific type of IVF protocol. These cases should be investigated to determine the most likely etiologies of the condition, as this is a complex problem with several variables. There are multiple risk factors for recurrent implantation failure including advanced maternal age, smoking status of both parents, elevated body mass index, and stress levels. Immunological factors such as cytokine levels and presence of specific autoantibodies should be examined, as well as any infectious organisms in the uterus leading to chronic endometritis. Uterine pathologies such as polyps and myomas as well as congenital anatomical anomalies should be ruled out. Sperm analysis, pre-implantation genetic screening and endometrial receptivity should be considered and evaluated, and IVF protocols should be tailored to specific patients or patient populations. Treatment approaches should be directed toward individual patient cases. In addition, we suggest considering a new initial step in approach to patients with RIF, individualized planned activities to activate the brain's reward system in attempt to improve immunological balance in the body.     

The sociality–health–fitness nexus: synthesis,conclusions and future directions

This theme issue has highlighted the links between sociality, health and fitness in a broad range of organisms, and with approaches that include field and captive studies of animals, comparative and meta-analyses, theoretical modelling and clinical and psychological studies of humans. In this concluding chapter, we synthesize the results of these diverse studies into some of the key concepts discussed in this issue, focusing on risks of infectious disease through social contact, the effects of competition in groups on susceptibility to disease, and the integration of sociality into research on life-history trade-offs. Interestingly, the studies in this issue both support pre-existing hypotheses, and in other ways challenge those hypotheses. We focus on unexpected results, including a lack of association between ectoparasites and fitness and weak results from a meta-analysis of the links between dominance rank and immune function, and place these results in a broader context. We also review relevant topics that were not covered fully in this theme issue, including self-medication and sickness behaviours, society-level defences against infectious disease, sexual selection, evolutionary medicine, implications for conservation biology and selective pressures on parasite traits. We conclude by identifying general open questions to stimulate and guide future research on the links between sociality, health and fitness.     

Bacterial genomes in epidemiology—present and future

Sequence data are well established in the reconstruction of the phylogenetic and demographic scenarios that have given rise to outbreaks of viral pathogens. The application of similar methods to bacteria has been hindered in the main by the lack of high-resolution nucleotide sequence data from quality samples. Developing and already available genomic methods have greatly increased the amount of data that can be used to characterize an isolate and its relationship to others. However, differences in sequencing platforms and data analysis mean that these enhanced data come with a cost in terms of portability: results from one laboratory may not be directly comparable with those from another. Moreover, genomic data for many bacteria bear the mark of a history including extensive recombination, which has the potential to greatly confound phylogenetic and coalescent analyses. Here, we discuss the exacting requirements of genomic epidemiology, and means by which the distorting signal of recombination can be minimized to permit the leverage of growing datasets of genomic data from bacterial pathogens.     

Subunit structure and gene control of mouse NADP—malate dehydrogenase

The NADP-dependent malate dehydrogenase (MDH) in the supernatant fraction of mouse tissues is known to occur in two allelic forms which are electrophoretically distinguishable; each produces a single band in starch gel. We have investigated the subunit structure and synthesis of NADP—MDH through electrophoretic patterns obtained from several experimental sources. (1) Heterozygotes containing both alleles yield a five-banded pattern. The bands are in an approximate frequency of 1:4:6:4:1; the two extremes correspond to the pure types and the three intermediates are presumably hybrid enzymes. The NADP—MDH molecule therefore appears to be a tetramer. (2) In muscle heterokaryons of allophenic mice (with homozygous nuclei of each genotype within a common cytoplasm), hybrid enzymes are formed; they are not formed in other allophenic tissues. Therefore the gene at this locus codes only for monomeric subunits and the tetramer is assembled in a second step in the cytoplasm. Also, both genes must function in a nucleus when the locus is active (e.g., in F₁ uninucleated cells). (3) Dissociation in vitro of mixtures of both pure types of enzymes, followed by reassociation among fragments, leads to a three-banded pattern, even after repeated cycles. Thus the tetramer must cleave in a fixed plane, to form dimers, which reassociate, rather than in a random fashion to form monomers. The most likely interpretation is that mouse NADP—MDH is an example of the type of tetramer postulated by Monod et al. (1965) and termed isologous. The dimers are held symmetrically in the tetrameric conformation by relatively weak forces; the monomeric subunits comprising the dimer are held together by stronger forces.These investigations were supported by U.S.P.H.S. grants No. HD-01646, CA-06927, and FR-05539, and by an appropriation from the Commonwealth of Pennsylvania.     

Pollen selection — past,present and future

 A series of studies, recently reviewed, has established that approximately 60% of the structural genes which are expressed in the sporophytic portion of the angiosperm life cycle are also expressed and exposed to selection in the pollen. Given the haploidy and large population sizes of pollen grains, a substantial portion of the sporophytic genome could thus be periodically exposed to a bacterial type of mass screening. This extraordinary possibility is often subject to some skepticism which may, of course, be justified. However, recent attempts to apply models appear to be inappropriate in this context, in part because these attempts overlook an important source of genetic variation, and also because they assume fixed values for selection and fitness. More recently, studies of pollen/pollen interactions have suggested that what Linskens termed the ”programic phase” may represent an arena for important, and largely unexplored phenomena, some of which are discussed here. Received: 3 June 1996 / Revision accepted: 26 July 1996