Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type

Circumferential skin creases Kunze type (CSC-KT) is a specific congenital entity with an unknown genetic cause. The disease phenotype comprises characteristic circumferential skin creases accompanied by intellectual disability, a cleft palate, short stature, and dysmorphic features. Here, we report that mutations in either MAPRE2 or TUBB underlie the genetic origin of this syndrome. MAPRE2 encodes a member of the microtubule end-binding family of proteins that bind to the guanosine triphosphate cap at growing microtubule plus ends, and TUBB encodes a β-tubulin isotype that is expressed abundantly in the developing brain. Functional analyses of the TUBB mutants show multiple defects in the chaperone-dependent tubulin heterodimer folding and assembly pathway that leads to a compromised yield of native heterodimers. The TUBB mutations also have an impact on microtubule dynamics. For MAPRE2, we show that the mutations result in enhanced MAPRE2 binding to microtubules, implying an increased dwell time at microtubule plus ends. Further, in vivo analysis of MAPRE2 mutations in a zebrafish model of craniofacial development shows that the variants most likely perturb the patterning of branchial arches, either through excessive activity (under a recessive paradigm) or through haploinsufficiency (dominant de novo paradigm). Taken together, our data add CSC-KT to the growing list of tubulinopathies and highlight how multiple inheritance paradigms can affect dosage-sensitive biological systems so as to result in the same clinical defect.     

Two new <Emphasis Type="Italic">Corollospora</Emphasis> species and one new anamorph based on morphological and molecular data

Two new species of the genus Corollospora, namely, C. anglusa sp. nov. with its anamorph Varicosporina anglusa sp. nov. and C. portsaidica sp. nov., which were isolated from the coast of the Mediterranean Sea in Egypt, are described in this article based on morphological and molecular evidence. The two new species have one-septate ascospores. Corollospora anglusa resembles C. gracilis by having narrow one-septate hyaline ascospores; however, they differ in ascomata and ascospore dimensions and in pure culture characteristics. Single-ascospore culture of C. anglusa produces the conidia of its anamorph, whereas an anamorph has not been reported for C. gracilis. Varicosporina anglusa differs from the other two known Varicosporina species by having conidial branches that are filamentous, rectangularly branched, hypha like, and disarticulated into two- or one-celled fragments. Corollospora portsaidica is morphologically similar to C. cinnamomea, but the two species differ in the dimensions, shape, and ornamentation of the ascospores. The new Corollospora species were confirmed to be divergent from other similar Corollospora species based on phylogenetic analyses of partial sequences of the LSU rDNA region.     

Relation between leptin and estradiol levels in Egyptian lactating Arab mares during foaling heat

Sixteen Arab lactating mares belonging to Al-Zahraa Arab Horse Stud underwent two ultrasound examinations at 3 weeks interval starting from the day of demonstration of foaling heat. In addition, daily blood samples were collected from parturition until after exhibiting first postpartum estrus (day 11) with daily observation of estrous signs. Both leptin and estradiol hormones were assayed. Mean day of foaling heat was 8.9 ± 0.9 day. Most mares came in foaling heat during days 9 and 10 had high conception rate compared to those who came in estrus earlier or later. Estradiol levels were high after day of foaling then decrease after expression of foaling heat. But leptin levels increase from day 8 to day 10 compared to other days before and after the first ovulation. A significant positive correlation was found between estradiol and leptin (r = 0.58, p < 0.025). The positive correlation between leptin and estradiol led us to suggest that leptin hormone plays an important role in ovulation of the first postpartum estrus in mares.     

Differentiation of Fanconi anemia and aplastic anemia using mitomycin C test in Tunisia

Fanconi anemia (FA) is a recessive chromosomal instability syndrome that is clinically characterized by multiple symptoms. Chromosome breakage hypersensitivity to alkylating agents is the gold standard test for FA diagnosis. In this study, we provide a detailed laboratory protocol for accurate assessment of FA diagnosis based on mitomycin C (MMC) test. Induced chromosomal breakage study was successful in 171 out of 205 aplastic anemia (AA) patients. According to the sensitivity of MMC at 50 ng/ml, 38 patients (22.22%) were diagnosed as affected and 132 patients (77.17%) as unaffected. Somatic mosaicism was suspected in an 11-year-old patient with a FA phenotype. Twenty-six siblings of FA patients were also evaluated and five of them (19.23%) were diagnosed as FA. From this study, a standard protocol for diagnosis of FA was developed. It is routinely used as a diagnostic test of FA in Tunisia.     

Bacillus cereus adhesion: Real time investigation of the effect on the chemistry of industrial stainless steel

The initial microorganism adhesion on substrate is an important step for the biofilm formation. The surface properties of the stainless steel and B. cereus were characterized by the sessile drop technique. Moreover, the physicochemical properties of surface adhesion and the impact of bio adhesion to the stainless steel were determined at different time of contact (2, 4, 7, 9 and 24 h). The results showed that the strain was hydrophilic (Giwi = 3.37 mJ/m²), whereas the substratum has hydrophobic character (Giwi = ?57.6 mJ/m²). Stainless steel surface presents a weak electron-donor character (γ^? = 4.1 mJ/m²) conversely to B. cereus that presents an important parameter (γ^? = 31.6 mJ/m²). The bio adhesion was investigated at different time of contact. The data analysis after 2 h, confirmed the adhesion of B. cereus with an amount of 10 cfu/cm² which increased to 1.210⁴ cfu/cm² after 24 h. Interestingly, despite the difference of hydropohbicity, the interaction between B. cereus and substratum was favored by the thermodynamic aspect of adhesion (ΔG_adhesion < 0). Interestingly, the study of the effect of B. cereus adhesion on the stainless steel has revealed that, the substratum becomes hydrophilic (θ° = 41.3, ΔGiwi = 39.6 mJ/m²) and highly electron donor (Γ^? = 52.9 mJ/m²) after 2 h of bio adhesion.     

Influence of three rates of salinity on okra plants (Abelmoschus esculentus L.) infected with root-knot nematode in vivo

A greenhouse experiment was carried-out to evaluate the effect of three rates of salinity as abiotic stress on okra plants (Abelmoschus esculentus) infected with the root-knot nematode (Meloidogyne incognita) as biotic stress. Plant lengths and weights were significantly (p?≤?0.05) reduced except root weight and there was a positive correlation between increasing the salinity concentration from 0.1 to 0.3% and increasing the rate of reduction in plant criteria. The number of J2 in soil, galls, and eggmasses were decreased linked to increased salinity rate as compared to nematode control treatment. However, peroxidase and catalase activities were significantly reduced linked to increasing the salinity concentration from 0.1 to 0.3%. There was no significant difference between total phenols at all treatments. Meanwhile, there was no significant improvement in N, P, and K contents whereas photosynthetic pigments (a, b) and carotene were significantly (p?≤?0.05) reduced by nematode infection and increasing the salinity rate from 0.1 to 0.3%.     

Cyclooxygenase-2 single-nucleotide polymorphisms and hepatocellular carcinoma in Egypt

Hepatocellular carcinoma (HCC) is a worldwide neoplasm for which early diagnosis is difficult and the prognosis is usually poor. Overexpression of cyclooxygenase 2 (COX-2) has been suggested to be associated with hepatocarcinogenesis. Although several COX-2 inhibitors have been used in hepatoma therapy, the genetic background between COX-2 and HCC remains largely unknown. In this study, the association of genotypic polymorphisms in COX-2 with HCC was investigated. 25 healthy individuals served as control (group I), group II: 50 HCV infection patients without any complications, group III: 50 HCV infected patients complicated with cirrhosis and group IV: 75 HCV infected patients complicated with (45 localized and 30 metastatic) HCC from Zagazig University Hospital in Egypt were genotyped by a PCR–RFLP method. The results showed that, no differences in distribution between the HCC and other groups were found. We found ?1195A allele carriers had a higher risk of HCC with HCV infection. As regard the obtained results of serum AFU, a significant increase was detected in HCC as compared with cirrhosis, hepatitis and healthy control groups (p < 0.001). Concerning the obtained results of serum AFP, when HCC group was compared with cirrhosis, hepatitis and healthy controls, a significant increase was observed (p < 0.001). In conclusion: identification of SNP in COX-2 gene promoter and evaluation of serum AFU and AFP give a red light in early detection of HCC which may be reduce its fatal incidence.     

In Vitro Evaluation of a Soluble Leishmania Promastigote Surface Antigen as a Potential Vaccine Candidate against Human Leishmaniasis

PSA (Promastigote Surface Antigen) belongs to a family of membrane-bound and secreted proteins present in several Leishmania (L.) species. PSA is recognized by human Th1 cells and provides a high degree of protection in vaccinated mice. We evaluated humoral and cellular immune responses induced by a L. amazonensis PSA protein (LaPSA-38S) produced in a L. tarentolae expression system. This was done in individuals cured of cutaneous leishmaniasis due to L. major (CCLm) or L. braziliensis (CCLb) or visceral leishmaniasis due to L. donovani (CVLd) and in healthy individuals. Healthy individuals were subdivided into immune (HHR-Lm and HHR-Li: Healthy High Responders living in an endemic area for L. major or L. infantum infection) or non immune/naive individuals (HLR: Healthy Low Responders), depending on whether they produce high or low levels of IFN-γ in response to Leishmania soluble antigen. Low levels of total IgG antibodies to LaPSA-38S were detected in sera from the studied groups. Interestingly, LaPSA-38S induced specific and significant levels of IFN-γ, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-α in more. No significant cytokine response was observed in individuals immune to L. braziliensis or L. donovani infection. Phenotypic analysis showed a significant increase in CD4+ T cells producing IFN-γ after LaPSA-38S stimulation, in CCLm. A high positive correlation was observed between the percentage of IFN-γ-producing CD4+ T cells and the released IFN-γ. We showed that the LaPSA-38S protein was able to induce a mixed Th1 and Th2/Treg cytokine response in individuals with immunity to L. major or L. infantum infection indicating that it may be exploited as a vaccine candidate. We also showed, to our knowledge for the first time, the capacity of Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infection.