Novel chimaeric protein expressed in Philadelphia positive acute lymphoblastic leukaemia

Cytogenic changes are becoming increasingly important in understanding the pathogenesis of human malignancies. The t(9;22) (q34;q11) translocation is one of the most consistent and generates the Philadelphia chromosome (Ph1) (ref. 1) in chronic myeloid leukaemia (CML); it has also been observed in some acute lymphoblastic leukaemias (ALL) (ref. 2). In CML the breakpoints occur on chromosome 22 in the region designated bcr (ref. 3) and result in the expression of a bcr-abl fusion product of relative molecular mass (MT) 210,000 (210K) with associated in vitro tyrosine kinase activity (P210bcr-abl). In some cases of Ph1-positive ALL, a novel abl-related protein (P190all-abl) of 190K has been shown to have tyrosine kinase activity. In this report we demonstrate that the P190all-abl protein has a bcr determinant from the amino-terminal region, but is lacking a bcr determinant normally found in the P210bcr-abl near the bcr-abl junction. The chimaeric nature of the P190all-abl was confirmed by sequential immunoprecipitation with antisera against abl and bcr peptides.     

Alpha-lactalbumin possesses a novel calcium binding loop

Calcium performs a unique role in biology, achieving biological effects through highly specific interactions with and modulation of target proteins. It has been proposed that calcium-modulated proteins possess a characteristic, evolutionarily related, binding fold, known as the EF-hand. The high-resolution X-ray structure of alpha-lactalbumin reveals a Ca2+ binding fold that resembles an EF-hand only superficially and presumably has no evolutionary relationship with it. However, there is clear homology with the corresponding loop in c-type lysozyme (the 'parent' molecule of alpha-lactalbumin). This study, at 1.7 A resolution, represents one of the most accurate analyses of a calcium binding protein yet reported.     

Early Homo erectus skeleton from west Lake Turkana, Kenya

The most complete early hominid skeleton ever found was discovered at Nariokotome III, west Lake Turkana, Kenya, and excavated in situ in sediments dated close to 1.6 Myr. The specimen, KNM-WT 15000, is a male Homo erectus that died at 12 +/- 1 years of age, as judged by human standards, but was already 1.68 m tall. Although human-like in many respects, this specimen documents important anatomical differences between H. erectus and modern humans for the first time.     

HIV infection is blocked in vitro by recombinant soluble CD4

The T-cell surface glycoprotein, CD4 (T4), acts as the cellular receptor for human immunodeficiency virus, type 1 (HIV-1), the first member of the family of viruses that cause acquired immunodeficiency syndrome. HIV recognition of CD4 is probably mediated through the virus envelope glycoprotein (gp120) as shown by co-immunoprecipitation of CD4 and gp120 (ref.5) and by experiments using recombinant gp120 as a binding probe. Here we demonstrate that recombinant soluble CD4(rsT4) purified from the conditioned medium of a stably transfected Chinese hamster ovary cell line is a potent inhibitor of both virus replication and virus-induced cell fusion (syncytium formation). These results suggest that rsT4 is sufficient to bind HIV, and that it represents a potential anti-viral therapy for HIV infection.     

The biology of streams as part of Amazonian forest ecology

Summary Data on long-term research on the ecology of Central Amazonian forest streams are presented and they reveal the following basic features: Firstly, the essential input of nutrients into these waters consists of forest litter and of the fungi that decompose this litter; consequently, the bulk of the fauna is concentrated in accumulations of submerged litter. Secondly, the nutrients released by the decomposition of this litter do not appear in solution in the stream water, but are tied up throughout in the food web of the aquatic fauna. Thirdly, this food web is relatively robust. This is due to the absence of food specialists in the major channels of energy transfer. One of the staple foods for invertebrate predators consists of chironomid larvae. Fourthly, the degree of acidity and/or the content of dissolved humic substances (more or less black water) has a marked effect on the density and to a lesser extent on the species diversity of the invertebrate fauna, black waters being richer in both. Fifthly, the annual inundations of the forest in the middle and lower courses of the smaller rivers lead to drastic periodic changes of animal densities, and in some cases to annual periodicity of breeding, as exemplified by a three-year study of shrimp populations in the river Tarumazinho.     

Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1

Epigenetic inheritance in mammals is characterized by high-fidelity replication of CpG methylation patterns during development. UHRF1 (also known as ICBP90 in humans and Np95 in mouse) is an E3 ligase important for the maintenance of global and local DNA methylation in vivo. The preferential affinity of UHRF1 for hemi-methylated DNA over symmetrically methylated DNA by means of its SET and RING-associated (SRA) domain and its association with the maintenance DNA methyltransferase 1 (DNMT1) suggests a role in replication of the epigenetic code. Here we report the 1.7 A crystal structure of the apo SRA domain of human UHRF1 and a 2.2 A structure of its complex with hemi-methylated DNA, revealing a previously unknown reading mechanism for methylated CpG sites (mCpG). The SRA-DNA complex has several notable structural features including a binding pocket that accommodates the 5-methylcytosine that is flipped out of the duplex DNA. Two specialized loops reach through the resulting gap in the DNA from both the major and the minor grooves to read the other three bases of the CpG duplex. The major groove loop confers both specificity for the CpG dinucleotide and discrimination against methylation of deoxycytidine of the complementary strand. The structure, along with mutagenesis data, suggests how UHRF1 acts as a key factor for DNMT1 maintenance methylation through recognition of a fundamental unit of epigenetic inheritance, mCpG.     

How Systemic Inquiry Releases Citizen Knowledge to Reform Schools: Community Scorecard Case Studies

Despite the relevance of systemic practice for repairing broken public systems, documented instances where it empowers marginalised groups en masse to be action researchers are rare. Public school systems that fail to educate millions of pupils are ripe for systemic inquiry. Using evidence, this article identifies conditions under which such inquiry fosters school system accountability and increases pupil learning. By tracing the emergence of a type of community scorecard practice called Citizen Voice and Action (CV&A), it explains how and why marginalised groups use CV&A’s systems-enhanced participatory research to engage with and reform unresponsive public systems. It also shows how soft systems thinking and further action research enhanced scorecard methodology. Brief case studies of CV&A use in Ugandan primary schools illustrate and explain how communities reform schools by using CV&A to systematically foster accountability. Discussion identifies how processes free them to create and use systemic knowledge. This theorising helps explain conditions under which systemic inquiry into school and other public systems is being generalised and scaled up.