Greig syndrome associated with an interstitial deletion of 7p: confirmation of the localization of Greig syndrome to 7p13

Summary An 11-month-old infant with Greig cephalopolysyndactyly syndrome and mild developmental delay is described. High-resolution chromosomal analysis showed a de novo interstitial deletion of chromosome 7p with breakpoints located at p13 and p14. Cytogenetic analysis of polymorphisms of the heterochromatin in the pericentromeric region suggested the deleted chromosome was of paternal origin. This case confirms the localization of Greig syndrome to 7p13 and emphasizes the importance of performing cytogenetic studies on patients with Mendelian disorders who have unusual findings or cognitive abnormalities in a disorder usually associated with normal intellect. Review of clinical features in published reports of patients with a deletion involving 7p13 showed a number to have features overlapping with Greig syndrome. Because of this, we suggest that cytogenetic aberrations, particularly chromosomal microdeletions, may represent a significant etiology for Greig syndrome.     

Aromatic-aromatic interactions in structures of proteins and protein-DNA complexes: a study based on orientation and distance

Interactions between the aromatic amino acid residues have a significant influence on the protein structures and protein-DNA complexes. These interactions individually provide little stability to the structure; however, together they contribute significantly to the conformational stability of the protein structure. In this study, we focus on the four aromatic amino acid residues and their interactions with one another and their individual interactions with the four nucleotide bases. These are analyzed in order to determine the extent to which their orientation and the number of interactions contribute to the protein and protein-DNA complex structures.     

Paxillin phosphorylation at Ser273 localizes a GIT1-PIX-PAK complex and regulates adhesion and protrusion dynamics

Continuous adhesion formation and disassembly (adhesion turnover) in the protrusions of migrating cells is regulated by unclear mechanisms. We show that p21-activated kinase (PAK)-induced phosphorylation of serine 273 in paxillin is a critical regulator of this turnover. Paxillin-S273 phosphorylation dramatically increases migration, protrusion, and adhesion turnover by increasing paxillin-GIT1 binding and promoting the localization of a GIT1-PIX-PAK signaling module near the leading edge. Mutants that interfere with the formation of this ternary module abrogate the effects of paxillin-S273 phosphorylation. PAK-dependent paxillin-S273 phosphorylation functions in a positive-feedback loop, as active PAK, active Rac, and myosin II activity are all downstream effectors of this turnover pathway. Finally, our studies led us to identify in highly motile cells a class of small adhesions that reside near the leading edge, turnover in 20-30 s, and resemble those seen with paxillin-S273 phosphorylation. These adhesions appear to be regulated by the GIT1-PIX-PAK module near the leading edge.     

Chemical characterization and quantification of siderophores produced by marine and terrestrial aspergilli

Ten aspergilli (five each from marine and terrestrial habitats) were screened for siderophore production. All test isolates produced siderophores as indicated by a positive reaction in the FeCl(3) test, chrome azurol sulphonate assay, and chrome azurol sulphonate agar plate test. Further, the test isolates were compared for their siderophore production potential and chemical characteristics. Examination of the chemical nature of the siderophores revealed that all test isolates produced hydroxamate siderophores that were trihydroxamate hexadentates. Wide-spread occurrence of siderophores in marine isolates indicate their functional role in maintaining overall productivity of coastal waters. Among all test aspergilli, marine Aspergillus versicolor was found to be the largest siderophore producer (182.5 microg/mL desferrioxamine mesylate equivalent), least siderophore production was recorded in a marine strain of Aspergillus niger (3.5 microg/mL desferrioxamine mesylate equivalent).     

Modest dietary K+ restriction provokes insulin resistance of cellular K+ uptake and phosphorylation of renal outer medulla K+ channel without fall in plasma K+ concentration

Extracellular K⁺ concentration ([K⁺]) is closely regulated by the concerted regulatory responses of kidney and muscle. In this study, we aimed to define the responses activated when dietary K⁺ was moderately reduced from a control diet (1.0% K⁺) to a 0.33% K⁺ diet for 15 days. Although body weight and baseline plasma [K⁺] (4.0 mM) were not reduced in the 0.33% K⁺ group, regulatory responses to conserve plasma [K⁺] were evident in both muscle and kidney. Insulin-stimulated clearance of K⁺ from the plasma was estimated in vivo in conscious rats with the use of tail venous and arterial cannulas. During infusion of insulin·(50 mU·kg^–1·min^–1), plasma [K⁺] level fell to 3.2 ± 0.1 mM in the 1.0% K⁺ diet group and to only 3.47 ± 0.07 mM in the 0.33% K⁺ diet group (P < 0.01) with no reduction in urinary K⁺ excretion, which is evidence of insulin resistance to cellular K⁺ uptake. Insulin-stimulated cellular K⁺ uptake was quantitated by measuring the K⁺ infusion rate necessary to clamp plasma K⁺ at baseline (in µmol·kg^–1·min^–1) during 5 mU of insulin·kg^–1·min^–1 infusion: 9.7 ± 1.5 in 1% K⁺ diet was blunted to 5.2 ± 1.7 in the 0.33% K⁺ diet group (P < 0.001). Muscle [K⁺] and Na⁺-K⁺-ATPase activity and abundance were unchanged during the 0.33% K⁺ diet. Renal excretion, which was measured overnight in metabolic cages, was reduced by 80%, from 117.6 ± 10.5 µmol/h/animal (1% K⁺ diet) to 24.2 ± 1.7 µmol/h/animal (0.33% K⁺ diet) (P < 0.001). There was no significant change in total abundance of key renal K⁺ transporters, but 50% increases in both renal PTK cSrc abundance and ROMK phosphorylation in the 0.33% K⁺ vs. 1% K⁺ diet group, previously established to be associated with internalization of ROMK. These results indicate that plasma [K⁺] can be maintained during modest K⁺ restriction due to a decrease in insulin-stimulated cellular K⁺ uptake as well as renal K⁺ conservation mediated by inactivation of ROMK, both without a detectable change in plasma [K⁺]. The error signals inciting and maintaining these responses remain to be identified. potassium homeostasis; Na⁺-K⁺-ATPase; H⁺-K⁺-ATPase; protein tyrosine kinase; cSrc     

Characterization of photosystem II heterogeneity in response to high salt stress in wheat leaves (<Emphasis Type="Italic">Triticum aestivum</Emphasis>)

The effect of high salt stress on PS II heterogeneity was investigated in wheat (Triticum aestivum) leaves. On the basis of antenna size, PS II has been classified into three forms, i.e., α, β, and γ centers while on the basis of electron transport properties of the reducing side of the reaction centers, two distinct forms of PS II have been suggested, i.e., Q_B reducing centers and Q_B non-reducing centers. The chlorophyll a (Chl a) fluorescence transients, which can quantify PS II behavior, were recorded using PEA to derive OJIP in vivo with high time resolution and further analyzed according to JIP test. Our results showed that with an increase in the salt concentration during growth, the number of Q_B non-reducing centers increased. In antenna size heterogeneity the number of β and γ centers increased while the number of α centers decreased. A change in the energetic connectivity between the PS II units was also observed. Recovery studies showed that antenna heterogeneity was completely recovered from damage at 0.5 M NaCl concentration and partially recovered at 1 M NaCl concentration while reducing side heterogeneity showed no recovery at all after 0.5 M onwards.     

Chlorophyll a fluorescence study revealing effects of high salt stress on Photosystem II in wheat leaves

In order to study the effects of high salt stress on PS II in detached wheat (Triticum aestivum) leaves, the seedlings were grown in Knop solution and temperature was 20 ± 2 °C. Detached leaves were exposed to high salt stress (0.1–0.5 M NaCl) for 1 h in dark and Chl a fluorescence induction kinetics was measured. Various parameters like Fv/Fm, ABS/RC, ETo/TRo, performance index and area over the florescence curve were measured and the energy pipeline model was deduced in response to salt stress. Our results show that the damage caused due to high salt stress is more prominent at the donor side rather than the acceptor side of PS II. Moreover the effects of high salt stress are largely reversible, as the acceptor side damage is completely recovered (～100%) while the recovery of the donor side is less than 85%. Based on our results we suggest that in response to high salt stress, the donor side of PS II is affected more as compared to the acceptor side of PS II.     

Effect of Glycation of Hemoglobin on its Interaction with Trifluoperazine

Trifluoperazine (TFZ), a phenothiazine drug, penetrates into human erythrocytes and releases oxygen by interaction with hemoglobin. TFZ-induced oxygen release from hyperglycemic erythrocytes isolated from diabetic patients is considerably less compared to that from the cells of normoglycemic individuals. In diabetes mellitus, hemoglobin is significantly glycated by glucose. Non-glycated hemoglobin, HbA₀ and its major glycated analog, HbA_1c have been separated from the blood samples of diabetic patients. TFZ releases considerable amount of oxygen from HbA₀, but very little from HbA_1c. Spectrofluorimetric studies reveal that TFZ forms excited state complexes with both HbA₀ and HbA_1c. Titration of HbA₀ with TFZ in a spectrophotometric study exhibits two isosbestic points. Similar experiment with HbA_1c causes gradual loss of the Soret peak without appearance of any isosbestic point indicating a possibility of heme loss during interaction, which is also supported by gel filtration experiment and SDS-PAGE experiment followed by heme staining. The results suggest that drug action on hemoglobin is influenced by glycation-induced structural modification of the protein.