Structural aberrations of chromosome 18

Summary 3 cases of the 18q — syndrome, 2 boys and 1 girl, are presented, and a comparison with data from the literature is given. The following features are typical of the syndrome: short stature, mental retardation, muscular hypotonia, a peculiar dysmorphia of the face and ears, cryptorchidism and small scrotum in males, proximally implanted thumbs, tapering fingers, excess of whorls on the fingertips, and dorsally implanted second toes. Midface hypoplasia with hypertelorism and cleft palate, as well as strabismus, were present in 2 of our patients, whereas all 3 showed nystagmus and prominence of anthelix and antitragus. In addition, 2 patients exhibited narrow ear canals and impaired hearing. One patient had coloboma of the iris and choroid, pale optic discs, and cleft lip; another had umbilical and inguinal hernias. Two cases represented de novo deletions of the long arm of chromosomes 18, whereas the karyotype of the father of the third case revealed a balanced translocation t(15;18)(q24;q21).

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Zusammenjassung 3 Patienten mit dem 18q — Syndrom, 2 Knaben und 1 Mädchen, werden vorgestellt und mit den Fällen der Literatur verglichen. Die folgenden typischen Merkmale des 18q — Syndroms fanden sich bei ihnen: Kleinwuchs, Schwachsinn, muskuläre Hypotonie, Gesichts- und Ohrdysmorphie, Kryptorchismus bei den Knaben sowie zurückversetzte Daumen, konisch zulaufende Finger, Häufung von Wirbelmustern auf den Fingerbeeren und nach dorsal versetzte 2. Zehen. 2 Patienten zeigten die für das 18q — Syndrom typische Mittelgesichtsdysplasie sowie Hypertelorismus und Strabismus, hingegen wiesen alle drei Nystagmus und eine charakteristische Ohrdysmorphie mit Vortreten von Anthelix und Antitragus auf. Je 2 Patienten waren schwerhörig bzw. hatten auffallend enge Gehörgänge. Bei einem Fall fanden sich noch ein Iris- und Chorioideakolobom, Opticusatrophie und eine Lippenspatle, bei einem anderen eine Nabel- und Leistenhernie. Bei 2 Patienten war die Deletion des langen Arms von Chromosome 18 neu entstanden, bei einem war der Vater Träger einer balancierten Translokation t(15;18)(q24;q21).

     

Mitoses and binucleated cells in perinatal human hearts

Cells from hardened formalin-fixed human hearts were isolated with potash lye. In perinatal hearts mitoses and evidence of irregular chromosomal movement such as chromatin bridges and micronuclei were observed in small numbers during normal development. A quantitative analysis of binucleated cells shows 8.8 +/- 5.3% in the left and 11.7 +/- 4.0% in the right ventricular wall around the time of birth. The number increases during the first year of life to 56.8 +/- 17.4% in the left and 42.0 +/- 18.1% in the right heart. This development precedes normal polyploidisation of the human heart by years.     

Native-like folding intermediates of homologous ribonucleases

The mechanism of the slow refolding reactions of four different pancreatic ribonucleases from ox, sheep, red deer, and roe deer has been investigated. Refolding kinetics of these proteins were very similar. In particular, a native-like intermediate, IN, was shown to be populated on the slow refolding pathway of all ribonucleases. We conclude that, similar to the stability of the folded proteins, the pathway of slow refolding has been conserved despite the differences in amino acid sequence and the varying number of proline residues.     

Exploring biological classification: The unique organism project

The unique organism project was designed as a culminating assessment for a biological classification unit in a middle school setting. Students developed a model to represent their unique organism. Using the model, students were required to demonstrate how their unique organism interacts with its environment, and how its internal and external structure and organization allowed it to carry out those interactions. The NGSS Cross Cutting Concepts of structure and function, systems, and system models along with the Science & Engineering Practice of constructing models were integrated and emphasized throughout the unit.     

Diaryl Disulfides as Novel Stabilizers of Tumor Suppressor Pdcd4

The translation inhibitor and tumor suppressor Pdcd4 was reported to be lost in various tumors and put forward as prognostic marker in tumorigenesis. Decreased Pdcd4 protein stability due to PI3K-mTOR-p70^S6K1 dependent phosphorylation of Pdcd4 followed by β-TrCP1-mediated ubiquitination, and proteasomal destruction of the protein was characterized as a major mechanism contributing to the loss of Pdcd4 expression in tumors. In an attempt to identify stabilizers of Pdcd4, we used a luciferase-based high-throughput compatible cellular assay to monitor phosphorylation-dependent proteasomal degradation of Pdcd4 in response to mitogen stimulation. Following a screen of approximately 2000 compounds, we identified 1,2-bis(4-chlorophenyl)disulfide as a novel Pdcd4 stabilizer. To determine an initial structure-activity relationship, we used 3 additional compounds, synthesized according to previous reports, and 2 commercially available compounds for further testing, in which either the linker between the aryls was modified (compounds 2–4) or the chlorine residues were replaced by groups with different electronic properties (compounds 5 and 6). We observed that those compounds with alterations in the sulfide linker completely lost the Pdcd4 stabilizing potential. In contrast, modifications in the chlorine residues showed only minor effects on the Pdcd4 stabilizing activity. A reporter with a mutated phospho-degron verified the specificity of the compounds for stabilizing the Pdcd4 reporter. Interestingly, the active diaryl disulfides inhibited proliferation and viability at concentrations where they stabilized Pdcd4, suggesting that Pdcd4 stabilization might contribute to the anti-proliferative properties. Finally, computational modelling indicated that the flexibility of the disulfide linker might be necessary to exert the biological functions of the compounds, as the inactive compound appeared to be energetically more restricted.     

Human Serotonin Transporter Expression During Megakaryocytic Differentiation of MEG-01 Cells

The serotonin (5-HT) transporter (SERT) has been found altered in platelets of patients with genetically complex disorders, including mood-anxiety, pain and eating disorders. In this study, we used cell cultures of platelet precursors as models of investigation on mechanisms of SERT regulation: SERT expression was appraised during megakaryocytic differentiation of human megakaryoblastic MEG-01 cells. Cells were cultured for 8 days with 10^?7M 4-β-12-tetradecanoylphorbol-13-acetate (β-TPA) in the presence of 10% fetal bovine serum (FBS) and SERT was assessed by real time PCR, immunofluorescence microscopy, Western blot and [³H]5-HT re-uptake. Results revealed that SERT is present in control-untreated MEG-01 cells. β-TPA-differentiating MEG-01 cells showed a redistribution of SERT fluorescence, diffuse to cell bodies and blebs along with a 3-fold SERT mRNA increase and a moderate raise in SERT protein (1.5/1.4-fold) by immunoblot and re-uptake assays. In summary, we have shown herein that control megakaryoblasts express the SERT protein. SERT is modulated by differentiation events, implying that SERT density in platelets is under the control of megakaryocytopoiesis stages. Differentiation of MEG-01 cells can provide considerable insight into interactions between SERT genetics, transmitter-hormonal/homeostatic mechanisms and signaling pathways.     

Responses of macroalgae to CO2 enrichment cannot be inferred solely from their inorganic carbon uptake strategy

Increased plant biomass is observed in terrestrial systems due to rising levels of atmospheric CO₂, but responses of marine macroalgae to CO₂ enrichment are unclear. The 200% increase in CO₂ by 2100 is predicted to enhance the productivity of fleshy macroalgae that acquire inorganic carbon solely as CO₂ (non‐carbon dioxide‐concentrating mechanism [CCM] species—i.e., species without a carbon dioxide‐concentrating mechanism), whereas those that additionally uptake bicarbonate (CCM species) are predicted to respond neutrally or positively depending on their affinity for bicarbonate. Previous studies, however, show that fleshy macroalgae exhibit a broad variety of responses to CO₂ enrichment and the underlying mechanisms are largely unknown. This physiological study compared the responses of a CCM species (Lomentaria australis) with a non‐CCM species (Craspedocarpus ramentaceus) to CO₂ enrichment with regards to growth, net photosynthesis, and biochemistry. Contrary to expectations, there was no enrichment effect for the non‐CCM species, whereas the CCM species had a twofold greater growth rate, likely driven by a downregulation of the energetically costly CCM(s). This saved energy was invested into new growth rather than storage lipids and fatty acids. In addition, we conducted a comprehensive literature synthesis to examine the extent to which the growth and photosynthetic responses of fleshy macroalgae to elevated CO₂ are related to their carbon acquisition strategies. Findings highlight that the responses of macroalgae to CO₂ enrichment cannot be inferred solely from their carbon uptake strategy, and targeted physiological experiments on a wider range of species are needed to better predict responses of macroalgae to future oceanic change.