Nucleation and growth of fibres and gel formation in sickle cell haemoglobin

Deoxygenated sickle haemoglobin polymerizes into long 210-A diameter fibres that distort and decrease the deformability of red blood cells, and cause sickle cell disease. The fibres consist of seven intertwined double strands. They can form birefringent nematic liquid crystals (tactoids) and spherulites. Rheologically, the system behaves as a gel. The equilibria show a phase separation and a solubility. The reaction kinetics show a delay time, are then roughly exponential and are highly dependent on concentration and temperature, and accord with the double nucleation model. But these conclusions are derived from macroscopic data, without direct observation of individual fibres. We have now used non-invasive video-enhanced differential interference contrast (DIC) and dark-field microscopy to observe nucleation, growth and interaction of sickle deoxyhaemoglobin fibres in real time. The fibres originate both from centres that produce many radially distributed fibres and on the surface of pre-existing fibres, from which they then branch. The resulting network is cross-linked and dynamic in that it is flexible and continues to grow and cross-link. Our results support most aspects of the double nucleation model.     

A haemoglobin switching activity modulates hereditary persistence of fetal haemoglobin

During human development there is a switch from fetal to adult haemoglobin formation, reflecting the differential expression of fetal (G gamma and A gamma) and adult (beta and delta) globin genes. Mutations that inhibit this switch produce variants of the syndrome of hereditary persistence of fetal haemoglobin (HPFH). Adult heterozygotes for these mutants produce 15-30% fetal haemoglobin (HbF) in their red cells. The general assumption is that the mutations result in a permanent switching on of gamma-globin genes. Here, however, we show that fetal globin expression can be turned off in cultures of HPFH cells by an uncharacterized factor in fetal sheep serum. This is the first demonstration that mutations affecting the developmental expression of globin genes can be modulated by exogenous factors. The findings raise the possibility that the phenotype of HPFH is not simply the direct result of mutations in or around globin genes but the consequence of the mutations on the interaction of globin genes with trans-acting regulatory factors.     

Centrifugal fibres synapse on dopaminergic interplexiform cells in the teleost retina

In teleost fish, centrifugal fibres originating in the olfactory bulb and containing FMRFamide-like and luteinizing hormone releasing hormone (LHRH)-like peptides project to the retina and terminate along the border of the inner nuclear and inner plexiform layers. Using a novel simultaneous two-colour immunolabelling technique, we have found that these centrifugal fibres are often closely apposed to the dopaminergic interplexiform cells. Contacts between centrifugal fibres and dopaminergic interplexiform cells were observed by electron microscopy to be conventional type synaptic junctions. Since the dopaminergic interplexiform cells make synapses on horizontal and bipolar cells, providing an intraretinal centrifugal pathway for information flow from the inner to the outer plexiform layers, we conclude that every neuron in the teleost retina is potentially susceptible to central influences via these centrifugal fibres and dopaminergic interplexiform cells.     

关于图的容错直径和宽直径

容错直径和宽直径是度量网络可靠性和有效性的重要参数。对任何k连通图，它的容错直径Dk不超过宽直径dk。论文证明d2≤max{(d1-1)(D2-1/2d1-1) 1,D2 1}；给出d1=2时d2=D2 1的一个充分必要条件：d2=3或d2=4且达到d2值的任何两顶点必相邻。     

Electrostatic interactions in the assembly of haemoglobin

Haemoglobin is the prototype of an allosteric protein in which cooperative behaviour depends on interaction between unlike subunits. Here we present haematological and biochemical evidence that electrostatic interactions are an important determinant of haemoglobin assembly. Individuals heterozygous for positively charged beta-globin variants have a significantly lower proportion of abnormal haemoglobin than those with negatively charged variants. Moreover, these differences become more pronounced when alpha-thalassaemia is also present. Kinetic experiments using isolated chains indicate that the rate of assembly of the heterotetramer is influenced by alterations in surface charge. A simple electrostatic model is proposed in an attempt to explain these haematological and experimental findings.     

图像法快速测量色斑直径和雨滴直径

采用图像法处理滤纸色斑测量雨滴直径。应用距离变换生成分水岭,以分水岭对滤纸色斑进行分割,获取滤纸上色斑面积,计算色斑等效直径D,率定自然雨滴直径d=1.1~4.1 mm,与色斑直径关系d=0.356 1×D0.723 3。图像法不受色斑毛刺影响,色斑等效直径测量准确,工作效率高。