The essence of phase transitions in condensed matter by an information theoretic approach.

Our information theoretic considerations suggest that the essence of phase transitions in condensed matter is the change in entropy as reflected in the change in the number of isomers between two phases. The explicit number of isomers as a function of size is computed using a graph theoretic approach that is compared to a direct count for smaller systems. This allows us to apply a common approach to both nanosystems and their macroscopic limit. The entropy increases very rapidly with size with the results that replacing the actual distribution over size by an average is not an accurate approximation. That the phase transition is a sharp function of the temperature is due to the high heat capacity of both the solid and liquid phases. The difference in entropy at the transition is related to the Trouton-Richards considerations. The finite width of the boundary between two phases of a finite system is related to the inherent uncertainty product that is derived from the maximum entropy formalism and that is a result of the fluctuations about equilibrium. As the system size increases, the boundary becomes sharper and one recovers the usual thermodynamic description.

Shortening sow restraint period during lactation improves production and decreases hair cortisol concentrations in sows and their piglets.

Food animal welfare is an issue of great concern, as society has a responsibility for animals under human care. Pork is the most consumed meat worldwide, with more than a billion pigs being slaughtered globally every year. Still, in most countries, sows are restrained in farrowing crates throughout lactation. In these crates, sows are confined with bars to an area that is just slightly larger than their body. Thus, moving and turning around, grooming, or expressing other natural behaviors are typically impossible. In this study, we utilized a simple and practical modification of conventional farrowing crates to designed farrowing pens, by removable confinement bars, which provide the flexibility to change the housing system from one to another. Our objective was to examine the parameters of production and hair cortisol concentrations after different restraint periods during lactation. Analyses included data from 77 sows and their 997 piglets. Sows were housed in farrowing crates, but the confinement bars were removed after different periods, from 3 days post-farrowing to full restraint. For certain analyses, sows were grouped into Short or Long Restraint groups (3-10 days vs 13-24 days, respectively). Multiple linear regression revealed that for any additional day in restraint of the sows, piglets' weaning rate decreases by 0.4% (P < 0.05). Moreover, the total number of weaned piglets per litter was higher in the Short Restraint group as compared to the Long Restraint group (10.4 ±â€¯0.3 vs 9.7 ±â€¯0.3, respectively; P < 0.05). Accordingly, total litter weight on the weaning day tended to be higher in the Short Restraint group (68.8 ±â€¯2.2 vs 64.9 ±â€¯1.8 kg; P = 0.1210). The requirement for medical treatments during lactation (e.g., antibiotics, NSAID) tended to be less frequent in the Short Restraint group (Sows: 21.9% vs 40%; P = 0.1219. Piglets: 2.4% vs 17.1%; P = 0.0609). Hair cortisol as a marker for chronic stress during lactation decreased when the restraint period was shortened in both sows and piglets. Our analysis revealed that sows' hair cortisol is a significant mediator between the restraint of the sow and its piglets' hair cortisol (Sobel test; P < 0.05). For every day of sows' restraint, sows' hair cortisol increased by 0.5 pg/mg, and for any additional unit of sows' hair cortisol, piglets' hair cortisol increased by 0.36 pg/mg. In conclusion, sustainable swine farming management can be beneficial for both animals and farmers; limiting sow restraint during lactation is expected to reduce stress, enhance welfare and production, and potentially improve the economics of swine operations.

Association of neutering with health and welfare of urban free-roaming cat population in Israel, during 2012-2014.

'Trap-Neutering by gonadectomy-Return' (TNR) is currently becoming an accepted method for managing free-roaming cat (FRC) populations, especially in human habitation. However, data regarding its impact on cat welfare are limited. In order to determine the demographic risk factors for FRC morbidity, we followed FRC populations in the city of Rishon LeZion during 2012-2014. Their age status (kitten/adult), contraceptive status (neutered/intact), sex, body-condition-scoring (BCS 1-5/5; 1= emaciation, 5= obesity), skin lesions, and external signs of disabilities and injuries were recorded and analyzed. We fitted a mixed effects generalized linear model to each cat-condition. Overall, 4615 cat-observations were recorded, of which 692 were kittens, 2365 neutered adults and 1445 intact adults. In comparison to intact adults, kittens had a significantly higher prevalence of emaciation (BCS 1; OR of 4.61, CI95% 2.67-7.6, p < 0.001) and severe disability or injury (OR of 3.65, CI95% 1.44-9.25, p = 0.006). Among adult cats, neutered cats had higher prevalence of obesity (BCS 5; OR 30.6, CI95% 10.06-93.09, p < 0.001), lower prevalence of skin lesions (OR of 0.51, CI95% 0.3-0.86, p = 0.011), and close to significant lower prevalence of severe disability or injury (OR of 0.4, CI95% 0.15-1.07, p = 0.068). However, these neutered adults also had a higher prevalence of permanent disability (e.g. anophthalmia, tail or limb absence) (OR of 1.67, CI95% 1.12-2.49, p = 0.012). A higher ratio of neutered FRCs in the geographical surroundings was correlated with a reduced prevalence of emaciated (BCS 1; OR of 0.85 for the increase of 10% in proportion of neutered cats, CI95% 0.74-0.97, p = 0.020) and thin adult cats (BCS 2; OR of 0.94 for the increase of 10% in proportion of neutered cats, CI95% 0.90-0.98, p = 0.010), among both neutered and intact cats. The results suggest that neutering has a favorable effect on FRC health. Such effect can be due to both a direct influence on the neutered cats themselves, as well as to an indirect effect on the general cat population (intact and neutered cats) by reducing competitive behavior of the neutered cats, which may enable other cats to gain additional access to vital resources. A higher prevalence of permanent disability found among the neutered FRCs does not necessarily represent a higher risk of injury but can rather be attributed to their potentially prolonged lifespan.

Post-partum concentrations of serum progesterone, oestradiol and prolactin in Arabian mares demonstrating normal maternal behaviour and Arabian mares demonstrating foal rejection behaviour.

The aim of this prospective study was to investigate possible endocrine components to foal rejection behaviour in post-partum Arabian mares. Arabian mares were divided into two groups based on their maternal behaviour: (1) mares with normal post-parturient behaviour (8 mares); and (2) mares that demonstrated foal-rejecting behaviour post-partum (15 mares). Most mares were visited and sampled twice, in the first and third days post-partum. Serum samples were used for measurement of progesterone, oestradiol and prolactin concentrations. There were no statistically significant differences in oestradiol, progesterone or prolactin concentrations between the groups. In the rejecting mares, there was a statistically significant decrease in the progesterone (mean±standard deviation, SD, 3.14±6.2ng/dL on day 1 and 0.49±0.18ng/dL on day 3) and prolactin (mean±SD 216.2±325.4ng/mL on day 1 and 145.2±311.4ng/mL on day 3) concentrations between days 1 and 3, while the oestradiol concentration did not change significantly. In the non-rejecting mares, progesterone concentrations decreased significantly (mean±SD 0.8±0.23ng/dL on day 1 and 0.43±0.22 on day 3) while the oestradiol and prolactin concentrations did not change significantly. The oestradiol to progesterone ratio was significantly higher in non-rejecting mares on day 1 (mean±SD 114.8±140.2 on day 1 and 143.4±72.6 on day 3) and this ratio increased significantly from days 1 to 3 in the rejecting mares (mean±SD 47.3±21.1 on day 1 and 122.1±123.7 on day 3).

Graphene Oxide Sheets Combine into Conductive Coatings by Direct Oxidative Electropolymerization.

New coatings are obtained when graphene oxide is further oxidized at moderate anodic potentials (≤~1.3 V vs. Ag/AgCl). Based on a variety of spectroscopic and electrochemical observations, the coatings are attributed to the direct electropolymerization of graphene oxide sheets via oxidation of the phenol edge groups on graphene. Depending on the applied potential, ether or carboxylic groups are formed. The coatings obtained via further oxidation are characterized by a lower O/C ratio due to decarboxylation and a higher content of C=C bonds. These bonds extend aromatic conjugation into the combined graphene oxide sheets and are responsible for the highly conductive nature of these coatings.

Nuisances and welfare of free-roaming cats in urban settings and their association with cat reproduction.

Free roaming cats (FRC) are highly abundant in cities around the world. Increasing populations of these cats might result in impairment of cat welfare and cause nuisances and public health risks. In order to study the seasonal dynamics of FRC populations and its association with events of cat welfare impairment and nuisances, we analyzed a database of FRC-associated citizens' telephone complaint events, which were registered in five cities in Israel (total human population of 1.42 million residents) during the years 2007-2011. These complaint events were classified to the following six categories: cat's carcasses, kittens, parturition, aggressive behavior toward people, invasion to human facilities, and cat injuries and distress. Overall, 87,764 complaint events associated with these categories were registered in the five cities during the study period (123.2 complaint events per 10,000 citizens per year). Length of daylight was moderately correlated with the rate of complaints on kittens in the same month (r=0.64) and parturition in the previous month (r=0.54) (P<0.001). Both kitten and parturition-related complaints showed a prominent seasonal pattern, peaking in April and May, respectively, and declining gradually until November. 'Kittens' or 'parturition' were explicitly mentioned in 38%, 39% and 19%, respectively, of the complaints regarding cat aggressiveness toward people, cat invasion to human facilities and cat injuries and distress. In most of the cities the rate of citizen complaints regarding carcasses, aggression, invasion and injuries were still significantly correlated with rate of complaints regarding kittens after omission of these joint complaints and remained significant after controlling for seasonality. These findings imply an association of cat welfare impairment and nuisances with FRC reproduction intensity. The current study revealed the high rate of nuisances and potential public health hazards related to FRC, as well as the impairment of cat welfare, which might be merely 'the tip of the iceberg' of the real welfare situation of these cats. Further studies should examine the effectiveness of FRC population control strategies for the reduction of the rate of nuisances and public health risks related to FRC, as well as for improving their welfare.

Recurrent, sequential, bilateral deep cerebellar hemorrhages: a case report.

INTRODUCTION: Hypertensive intra-cerebral hemorrhage is usually a one-time event and recurrences are rare. Most recurrences develop as part of long-term failure of blood pressure control. The site of the re-bleed is usually limited to the basal ganglia and thalami. CASE PRESENTATION: We report the case of a 59-year-old hypertensive Caucasian woman who developed two sequential, right- and then left-sided, deep cerebellar hemorrhages. The second hemorrhage followed the first one by 57 days, at a time when her blood pressure was optimally controlled. In spite of these critical sites and short duration between the two bleeds, the patient achieved a relatively good functional recovery. Her brain magnetic resonance angiogram was unremarkable. CONCLUSION: The development of recurrent hypertensive hemorrhage is rare and usually occurs within two years of the first bleed. To the best of our knowledge, this is the first reported case of bilateral, sequential, right- and then left-sided deep cerebellar hemorrhages. These hemorrhages were separated by eight weeks and the patient had a relatively good functional recovery. We believe that hypertension was the etiology behind these hemorrhages.

Folliculogenesis, embryo parameters and post-transfer recipient pregnancy rate following equine follicle-stimulating hormone (eFSH) treatment in cycling donor mares.

BACKGROUND: Induction of multiple ovulations, or superovulation, may potentially increase the efficiency of equine embryo transfer programs. Our objective was to investigate the effects of equine follicle-stimulating hormone (eFSH) treatment on the success rate of embryo transfer programs in mares. METHODS: In the research facility of the University of Saskatchewan, Canada, we studied 12 donor mares and 37 recipient mares during the physiological breeding season. Donor mares were used in two consecutive oestrous cycles: the first served as the control cycle and in the second an eFSH regimen was applied (eFSH cycle). In the control cycle, mares were administered human chorionic gonadotropin (hCG) to induce ovulation when a follicle ≥35 mm in diameter was detected by transrectal ultrasonographic examination. In the second oestrous cycle, twice-daily eFSH treatment was initiated when a follicle ≥25 mm was detected and treatment ceased when a follicle ≥35 mm was present, at which time hCG was administered. All donor mares were artificially inseminated while in oestrus using fresh semen collected from a stallion of proven fertility. At 8 days post-ovulation, embryos were recovered transcervically and transferred individually to the uterus of a synchronised recipient mare. RESULTS: The eFSH treatment stimulated the ovary and resulted in greater numbers of ovulations and recovered embryos; however the recovered embryos tended to have a lower morphological grade than the control embryos, and the recipient pregnancy rate per transferred embryo was lower than anticipated. CONCLUSION: The numbers of recipient pregnancies and foals born that resulted from eFSH treatment were not different from the control.

Ovulation, pregnancy rate and early embryonic development in vernal transitional mares treated with equine- or porcine-FSH.

The objective of this study was to compare the efficacy of purified equine- and porcine-FSH treatment regimes in mares in early vernal transition. Mares (n = 22) kept under ambient light were examined ultrasonographically per-rectum, starting January 30th. They were assigned to one of two treatment groups using a sequential alternating treatment design when a follicle >or= 25 mm was detected. In the eFSH group, mares were treated twice daily with equine-FSH, and in the pFSH group mares were treated twice daily with porcine-FSH; treatments were continued until follicle(s) >or= 35 mm, and 24 h later hCG was administered. Oestrous mares were inseminated with fresh semen and examined for pregnancy on days 11-20 post-ovulation. In the eFSH group, 11/11 (100%) mares developed follicle(s) >or= 35 mm, 8/11 (73%) ovulated and 6/8 (75%) conceived. In the pFSH group, 5/11 (45%) developed follicle(s) >or= 35 mm, 4/11 (36%) ovulated and 3/4 (75%) conceived. Treatment with eFSH resulted in a greater ovarian stimulation; higher number of pre-ovulatory-sized follicles, higher number of ovulations and higher number of embryos (p < 0.05). Following ovulation, serum progesterone concentrations were correlated with the number of CLs and supported early embryonic development; maternal recognition of pregnancy occurred in all pregnant mares. We concluded that eFSH can be used to effectively induce follicular growth and ovulation in vernal transitional mares; however, if bred, diagnosis and management of twins' pregnancies would be required prior to day 16 because of the increased risk of multiple embryos per pregnancy. Conversely, the current pFSH treatment regime cannot be recommended.

Semen characteristics in a sub-fertile Arabian stallion with idiopathic teratospermia.

A 5-year-old Arabian stallion was managed for breeding with fresh/extended semen during a period of 8 months with a resulting per cycle pregnancy rate of 26.3%. The stallion was in good health and no abnormalities of the reproductive tract were observed. Evaluation of several ejaculates revealed that sperm production and semen quality were mostly unchanged during the period of evaluation, that sperm production was normal and that semen quality was extremely poor. The most prevalent sperm defects were abnormal heads and mid-pieces. Most abnormal heads were microcephalic and/or tapered and considerable variation in sperm head dimensions within and among ejaculates was observed. A unique defect characterized by swollen/roughened mid-piece caused by accumulation of cytoplasmic-like material and abnormal mitochondrial sheath was observed. Nuclear vacuoles, acrosome defects, and teratoids were also prevalent and most sperm presented multiple abnormalities. The absence of any clear cause or any signs of testicular degeneration, combined with normal sperm production, and constant abnormal sperm production suggest an inherent, congenital disturbance of spermatogenesis as the cause of teratospermia in this case.

Efficiency of superovulation and in vivo embryo production in eFSH-treated donor mares after estrus synchronization with progesterone and estradiol-17beta.

Reliable methods of regulating estrus and stimulating superovulations in equine embryo transfer programs are desirable. Our objectives were to investigate the efficacy of a progesterone and estradiol-17beta (P&E) estrus synchronization regimen in mares with and without subsequent equine follicle-stimulating hormone (eFSH) treatment and to examine the effects of eFSH on folliculogenesis and embryo production. Cycling mares were treated with P&E daily for 10 d. On the final P&E treatment day, prostaglandin F(2alpha) was administered, and mares were randomly assigned to one of two treatment groups (n=20 mares/group). In both groups, mares were examined daily by transrectal ultrasonography. In the eFSH group, twice-daily eFSH treatments were initiated at follicle diameter 20 to 25 mm and ceased at follicle > or =35 mm; human chorionic gonadotrophin (hCG) was administered after 36 h. In the control group, eFSH treatments were not given, but hCG was administered at follicle > or =35 mm. Mares were inseminated with fresh semen, and embryo recovery attempts were performed 8 d postovulation. Synchrony of ovulations within each group appeared to be similar. Six mares in the eFSH group failed to ovulate. The eFSH treatment resulted in higher (P<0.05) numbers of preovulatory follicles and ovulations; however, embryo recovery rate did not increase (eFSH 1.0+/-0.4 vs. control 0.95+/-0.1 embryos/recovery attempt), and embryo per ovulation rate was significantly lower (36% vs. 73%). The eFSH-treated mares had significantly higher frequency of nonovulatory follicles (28% vs. 0) and higher periovulatory serum concentrations of estradiol-17beta. Based on our findings, combined P&E and eFSH regimens cannot be recommended for cycling donor mares.

Comparison of the effects of eFSH and deslorelin treatment regimes on ovarian stimulation and embryo production of donor mares in early vernal transition.

The objective was to compare the effects of eFSH and deslorelin treatment regimes on ovarian stimulation and embryo production of donor mares in early spring transition. Starting January 30th, mares kept under ambient light were examined by transrectal ultrasonography. When a follicle > or =25 mm was detected, mares were assigned to one of two treatment groups, using a sequential alternating treatment design. In the eFSH group, mares (n=18) were treated twice daily with eFSH (12.5mg im) until they achieved a follicle > or =35 mm; hCG was given 36 h later. In the deslorelin group, mares (n=18) were treated twice daily with deslorelin (63 microg im) until a follicle > or =35 mm was detected, and then they were given hCG. Estrous mares were inseminated with fresh semen. Eight days after ovulation, embryo recovery attempts were performed. In each group, 14/18 (78%) mares ovulated following the eFSH or deslorelin treatment regimes. The mean (95% CI) interval from treatment initiation to ovulation was 8.2d (7.3, 8.9) and 7.2d (6.2, 8.1) in the eFSH and deslorelin groups, respectively. In the eFSH group, the number of ovulations was significantly higher (mean+/-S.E.M.; 3.4+/-0.4 vs. 1.1+/-0.1 ovulations), and more embryos were recovered (2.6+/-0.5 vs. 0.4+/-0.2 embryos/recovery attempt). We concluded that eFSH and deslorelin treatment regimes were equally effective in inducing ovulation in early transitional mares, within a predictable time of treatment; however, the eFSH regime increased the number of ovulations and embryos recovered per mare.

Quantitative monitoring by polymerase colony assay of known mutations resistant to ABL kinase inhibitors.

Resistance to molecularly targeted chemotherapy, and the development of novel agents that are active against resistant forms of target proteins create the need for a sensitive and quantitative assay to monitor drug-resistant mutations in patients to guide treatment and assess response. Here, we describe an application of the polymerase colony (polony) method to identify and quantify known point mutations in the BCR-ABL oncogene in patients with chronic myelogenous leukemia who evolve resistance to ABL kinase inhibitors. The assay can detect mutations with a sensitivity of 10(-4), quantify the burden of drug-resistant cells, and simultaneously monitor the dynamics of several coexisting mutations. As a proof of concept, we analysed blood samples from three patients undergoing therapy with ABL kinase inhibitors and found that the patients' response to therapy correlated with our molecular monitoring. We were also able to detect mutations emerging in patients long before clinical relapse. Therefore, the polony assay could be applied to a larger patient sample to assess the utility of early mutation detection in patient-specific treatment decisions. Finally, this methodology could be a valuable research tool to shed light on the natural behavior of mutations pre-existing kinase inhibitors therapy and either disappearing over time or slowly taking over.

Increased growth of young citrus trees under reduced radiation load in a semi-arid climate.

This study investigated the effects of radiation heat-load reduction by shading on the growth and development of citrus trees in a warm subtropical region. The experiment was conducted from mid-June until late October when daily maximal air temperature averaged 29.3 degrees C. Two-year-old de-fruited Murcott tangor (Citrus reticulata BlancoxCitrus sinensis (L.) Osb.) trees were grown under 30% or 60% shade tunnels, or 60% flat shade (providing midday shade only), using highly reflective aluminized nets. Non-shaded trees were used as the control. Shading reduced direct more than diffuse radiation. Daily radiation was reduced by 35% for the 30% Tunnel and 60% Flat treatments, and by 55% for the 60% Tunnel. Two days of intensive measurement showed that shading increased average sunlit leaf conductance by 44% and photosynthesis by 29%. Shading did not significantly influence root and stem dry weight growth, but it increased the increment in leaf dry weight during the three month period by an average of 28% relative to the control, while final tree height in the 30% Tunnel treatment exceeded the control by 35%. Shoot to root and shoot mass ratios increased and root mass ratio decreased due to shading because of the increase in leaf dry weight. Shading increased starch concentration in leaves while the shadiest treatment, 60% Tunnel, decreased starch concentration in the roots. Carbon isotope ratio (delta(13)C) of exposed leaves that developed under shading was significantly reduced by 1.9 per thousand in the 60% Tunnel, indicating that shading increased CO(2) concentrations at the chloroplasts (C(c)), as would be expected from increased conductance. Substomatal CO(2) concentrations, C(i), computed from leaf net CO(2) assimilation rate and conductance values, also indicate that shading increases internal CO(2) concentrations. Based on tree dry mass, tree height, and total carbohydrates fractions, the 30% Tunnel and the 60% Flat were the optimal shade treatments.

The spectrum of mutations, including four novel ones, in the thiamine-responsive megaloblastic anemia gene SLC19A2 of eight families.

Thiamine responsive megaloblastic anemia (TRMA) is an autosomal recessive disorder with a triad of symptoms: megaloblastic anemia, deafness, and non-type 1 diabetes mellitus. Occasionally, cardiac abnormalities and abnormalities of the optic nerve and retina occur as well. Patients with TRMA often respond to treatment with pharmacological doses of thiamine. Recently, mutations were found in patients with TRMA in a thiamine transporter gene (SLC19A2). We here describe the mutations found in eight additional families. We found four novel mutations and three that were previously described. Of the novel ones, one is a nonsense mutation in exon 1 (E65X), two are missense mutations in exon 2 (S142F, D93H), and another is a mutation in the splicing donor site at the 5' end of intron 4 (C1223+1G>A). We also summarize the state of knowledge on all mutations found to date in TRMA patients. SLC19A2 is the first thiamine transporter gene to be described in humans. Reviewing the location and effect of the disease causing mutations can shed light on the way the protein functions and suggest ways to continue its investigation.

Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness.

Thiamine-responsive megaloblastic anaemia (TRMA), also known as Rogers syndrome, is an early onset, autosomal recessive disorder defined by the occurrence of megaloblastic anaemia, diabetes mellitus and sensorineural deafness, responding in varying degrees to thiamine treatment (MIM 249270). We have previously narrowed the TRMA locus from a 16-cM to a 4-cM interval on chromosomal region 1q23.3 (refs 3,4) and this region has been further refined to a 1.4-cM interval. Previous studies have suggested that deficiency in a high-affinity thiamine transporter may cause this disorder. Here we identify the TRMA gene by positional cloning. We assembled a P1-derived artificial chromosome (PAC) contig spanning the TRMA candidate region. This clarified the order of genetic markers across the TRMA locus, provided 9 new polymorphic markers and narrowed the locus to an approximately 400-kb region. Mutations in a new gene, SLC19A2, encoding a putative transmembrane protein homologous to the reduced folate carrier proteins, were found in all affected individuals in six TRMA families, suggesting that a defective thiamine transporter protein (THTR-1) may underlie the TRMA syndrome.

Refined mapping of the gene for thiamine-responsive megaloblastic anemia syndrome and evidence for genetic homogeneity.

Thiamine-responsive megaloblastic anemia (TRMA, also known as Rogers syndrome, OMIM 249270) is a rare autosomal recessive disorder characterized by a triad of megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Patients respond, to varying degrees, to treatment with megadoses of thiamine. We have recently shown genetic linkage of the TRMA gene to a 16-centimorgan (cM) region on 1q23.2-1q23.3 based on the analysis of four large, inbred families of Alaskan, Italian, and Israeli-Arab origin. Here we narrow the TRMA interval down to 4 cM based on genetic recombination, homozygosity mapping, and linkage disequilibrium (highest LOD score of 12.5 at D1S2799, at a recombination fraction of 0). We provide further evidence that the TRMA gene is located in this region and confirm the homogeneity of the disease. In this analysis, we genotyped seven additional families of diverse ethnic origin (Pakistani, Indian, Italian, Brazilian, and Japanese), and analyzed additional markers in two previously reported families showing evidence of linkage disequilibrium in a large area of their haplotypes. The multi-system manifestations of TRMA suggest that thiamine has a pivotal role in a multiplicity of physiological processes. Mapping the TRMA gene and understanding the molecular basis of the disease might, thus, shed light on the role of thiamine in common disorders such as deafness, anemia, and diabetes.

Mechanisms leading to cortical reaction in the mammalian egg.

Activation of the mammalian egg results in cortical reaction (CR), which is correlated with an increase in intracellular Ca2+ concentration and PKC activation. The CR is a gradual rather then an "all or none" response, and can be regulated by different concentrations of parthenogenetic activators. To evaluate the biological significance of parthenogenetic induced CR, rat eggs were fertilized or activated by different concentrations of ionomycin and TPA. Cortical granules (CG) were monitored by electron microscopy, while the CG exudate was visualized by Lens culinaris lectin and Texas Red, using light and confocal microscopy. The ability of the CR to trigger a full block to polyspermy was examined in an IVF system. Our study demonstrates the existence of light and dark CG, which differ by number, distribution in the egg cortex, and sensitivity to parthenogenetic activators. Sperm penetration or high concentration of activators, trigger depletion of both light and dark CG, leading to a full CR. Low concentration of activators altered the CG density, the ratio of dark/light CG, and induced partial CR that was sufficient to cause a block to polyspermy. The results imply that Ca2+ rise or PKC activation have different effects on light and dark CG. In recently fertilized or parthenogenetically activated eggs, CG exudate appeared as evenly distributed spots, whereas in more advanced stages of fertilization the exudate was scattered as patchy aggregates. This observation suggests a difference in the dispersion of CG exudate after fertilization as compared to parthenogenetic activation.