Biological effects of salinity gradient reversals in a southeast African estuarine lake

St Lucia Lake on the north coast of Natal, South Africa, has an area of 325 km² and is the largest estuarine complex in Africa. It consists of a 20 km tidal channel, averagingca. 400 m in width, linking the sea with the non-tidal lake which is H-shaped with a maximum length ofca. 40 km and width ofca. 20 km. Except during flood periods the depth of the lake does not exceed 2 m. The salinity gradient depends on evaporation, the configuration of the mouth and on the input of fresh water from four rivers which discharge into the northern and western areas of the lake. If fresh water input is high, the lake and much of the channel may be fresh. An intermediate stage features a normal salinity gradient while a third stage shows a reversed salinity gradient with salinities in excess of 100‰ in the upper reaches of the system. Changing salinities have marked effects on the biota. Aquatic macrophytes show cycles of appearance and disappearance depending on salinity tolerance and the presence of dormant stages. The resident benthic faunal species go through cycles of range expansion and contraction depending on prevailing salinities and recolonisation by dispersal phases. To date salinities in the southern part of the lake have approached, but not exceeded, lethal levels and this has therefore acted as a reservoir area. Catchment degradation and water abstraction are anticipated to exacerbate future salinity extremes. This has resulted in concern for the long term viability of this Ramsar site which has major southern African populations of hippopotamus and crocodile, provides breeding sites for South African Red Data water bird species and plays an important nursery role for marine fish and penaeid prawns.     

A differential proteomics study of cerebrospinal fluid from individuals with Niemann-Pick disease,Type C1

Niemann-Pick, type C1 (NPC1) is a fatal, neurodegenerative disease, which belongs to the family of lysosomal diseases. In NPC1, endo/lysosomal accumulation of unesterified cholesterol and sphingolipids arise from improper intracellular trafficking resulting in multi-organ dysfunction. With the proximity between the brain and cerebrospinal fluid (CSF), performing differential proteomics provides a means to shed light to changes occurring in the brain. In this study, CSF samples obtained from NPC1 individuals and unaffected controls were used for protein biomarker identification. A subset of these individuals with NPC1 are being treated with miglustat, a glycosphingolipid synthesis inhibitor. Of the 300 identified proteins, 71 proteins were altered in individuals with NPC1 compared to controls including cathepsin D, and members of the complement family. Included are a report of 10 potential markers for monitoring therapeutic treatment. We observed that pro-neuropeptide Y (NPY) was significantly increased in NPC1 individuals relative to healthy controls; however, individuals treated with miglustat displayed levels comparable to healthy controls. In further investigation, NPY levels in a NPC1 mouse model corroborated our findings. We posit that NPY could be a potential therapeutic target for NPC1 due to its multiple roles in the central nervous system such as attenuating neuroinflammation and reducing excitotoxicity.     

Purification of human leucocyte DNA: proteinase K is not necessary.

A rapid nontoxic method for the purification of DNA from human leucocytes is described. Preliminary experiments which tested different methods of DNA purification indicated that digestion of proteins with proteinase K was unnecessary. This led to the development of a simple procedure involving lysis of the cells in SDS followed by extraction with 6 M NaCl. The method described overcomes the requirement for lengthy incubations in the presence of expensive proteinase K and subsequent extraction with toxic chemicals.     

MITOCHONDRIAL GENOTYPES HAVE NO DETECTABLE EFFECTS ON MERISTIC TRAITS IN CUTTHROAT TROUT HYBRID SWARMS

Efforts to detect effects of cytoplasmic genes are confounded by the problem of partitioning nuclear and cytoplasmic effects. In this study we test for effects of mtDNA haplotype on development in hybrid populations of cutthroat trout (Oncorhynchus clarki) with randomly associated nuclear and mtDNA genotypes. We have previously described several intraspecific hybrid swarms formed by interbreeding of westslope cutthroat trout (O. c. lewisi) and Yellowstone cutthroat trout (O. c. bouvieri). Genetic distance between these subspecies is high (Nei's D = 0.30; mtDNA P = 0.02), and diagnostic alleles at multiple nuclear loci and two distinct mtDNA haplotypes are present in the hybrids. Historical associations between alleles at nuclear loci and between cytotypes and nuclear alleles have largely decayed. We test for differences in meristic characters between fish with alternate mtDNA haplotypes. Counts and fluctuating bilateral asymmetry for these characters have been previously shown to be sensitive indicators of genetic differences that affect development. No differences were found between mtDNA types in meristic counts or fluctuating asymmetry. Therefore, the alternate mtDNA haplotypes had no detectable effect on development as measured by meristic counts in these hybrid populations. However, diagnostic alleles at one nuclear allozyme locus (CK-CI) were associated with several fin ray counts.     

Immunogenicity, macrophage sensitivity, and therapeutic response to C. parvum of fibrosarcomas induced in C. parvum-treated and untreated mice

Summary No correlation has been observed between the therapeutic response of isogeneic transplants of methylcholanthrene-induced murine fibrosarcomas to Corynebacterium parvum (CP) and the sensitivity of the tumour cells to the cytotoxic action of CP-activated macrophages (Mø) in vitro. Neither of these parameters appeared to be influenced by repeated administration of CP during induction of the primary tumour or by whether the carcinogen was administered in solution or as crystals on a Millipore disc. On the other hand, tumours which developed in CP-treated mice after injection of a small dose (0.1 mg) of methylcholanthrene (MC) were more immunogenic than those which developed after the same dose of MC in untreated mice, as judged by the capacity of an injection of an irradiated tumour cell suspension to protect isogeneic mice against subsequent challenge with viable cells. Further work is needed to explain these findings.     

X-inactivation patterns in lymphocytes and skin fibroblasts of three cases of X-autosome translocations with abnormal phenotypes

Summary X-inactivation patterns were studied by replication analyses both in lymphocytes and skin fibroblasts of two patients carrying balanced X-autosome translocations, t(X;10)-(pter;q11) and t(X;17)(q11;q11), and one patient with an unbalanced translocation t(X;22)(p21;q11). Preferential late replication of the normal X chromosome was found in lymphocytes of both patients carrying balanced translocations and in skin fibroblasts of the patient carrying the translocation t(X;17). However, skin fibroblasts of the patient with a translocation t(X;10) showed preferential late replication of the abnormal der(X) chromosome with no spreading of late replication to the autosomal segment. In the case of unbalanced translocation t(X;22) there was preferential late replication of the der(X) chromosome both in lymphocytes and skin fibroblasts. The abnormal phenotype of the patients is discussed in relation to the observed X-inactivation patterns and the variability of the patterns in different tissues.     

Haemophilia A home therapy in the United Kingdom 1975-6.

Data on home treatment for patients with haemophilia A (factor VIII deficient haemophilia) were compiled for 1975 and 1976 from questionnaires answered by directors of haemophilia centres throughout the United Kingdom. There were 48 haemophilia centres in 1975 and 71 in 1976. The number of patients on or in training for home treatment increased from 267 to 488 in the two years, and a further 241 haemophiliacs were considered suitable for home therapy by the end of 1976. Apart from a small (but increasing) number of haemophiliacs on prophylactic treatment, most patients were on low-dose (250-500 units) on-demand regimens, using a mean of 20 000 factor VIII units per patient per year in 1976. An estimated 55% of the blood product used for home therapy in the UK in 1976 was imported from commercial sources. Despite the fact that the numbers of patients on home treatment have increased, so that about 60% of the potential population were receiving or being considered for home treatment in 1976, inadequacies in the service still remain. In some centres follow-up is clearly inadequate; about 15% of patients still rely on cryoprecipitate; and too little money has been invested in making the NHS self-sufficient in factor VIII production.     

Triassic environments, climates and reptile evolution

A consideration of all the available data on Triassic vertebrate faunas, and their stratigraphic location reveals a relatively sudden extinction event among the last of the mammal-like reptiles and the herbivorous rhynchosaurs in the Norian of the Upper Triassic. This event was apparently quickly followed by the radiation of the dinosaurs, also in the Norian. This conclusion suggests that competition was not the main factor in the initial success of the dinosaurs, but opportunistic radiation following the extinction of major reptile groups. A global review of Triassic sedimentary facies shows that there were climatic and floral changes towards the end of the Triassic. It is envisaged that increasing aridity in the later Triassic, resulting from plate motions and particularly affecting Gondwanaland and southwestern Laurasia, brought about floral changes and then the reptile extinctions. With the rapid evolution of new floras of conifers and bennettitaleans, the dinosaurs came to dominate all terrestrial faunas within the space of only a few million years.     

Structures located at the levels of the Z bands in mouse ventricular myocardial cells

Within ventricular myocardial cells of the mouse, the myoplasmic regions located immediately adjacent to the Z lines of the sarcomeres contain a variety of structures. These include: (1) transversely oriented 10 nm (‘intermediate’) filaments that apparently contribute to the cytoskeleton of the myocardial cell; (2) the majority of the transverse elements of the T-axial tubular system; (3) specialized segments of the sarcoplasmic reticulum (SR) that are closely apposed to the sarcolemma or T-axial tubules (junctional SR); (4) ‘extended junctional SR’ (‘corbular SR’) that exists free of association with the cell membrane; (5) ‘Z tubules’ of SR that are intimately apposed to the Z line substance; and (6) leptofibrils. In addition, fasciae adherentes supplant Z lines where myofibrils insert into the transverse borders (intercalated discs) of the cells. The concentration of these myocardial components at the level of the Z lines suggests that a particular specialization of structural and physiological activities exists in the Z-level regions of the myoplasm. In particular, it appears that the combination of intermediate filaments, T tubules, and Z-level SR elements forms a series of parallel planar bodies that extend across each myocardial cell to impart transverse rigidity. The movement and compartmentation of calcium ion (Ca²⁺) would seem especially active near the Z lines of the myofibrils, in view of the preferential location there of Ca²⁺-sequestering myocardial structures such as T tubules, junctional SR, extended junctional SR and Z tubules.     

Human natural cell-mediated cytotoxicity

Summary The contribution of natural cell-mediated cytotoxicity (NCMC) to tumor-directed cytotoxicity is unknown. This study was undertaken to correlate changes in NCMC to a single target cell (K-562) with responses to therapy in patients with small cell carcinoma of the lung, resectable stage I non-small cell carcinoma of the lung, and stage I and II melanomas. Data from these studies suggested that these patients have depressed levels of NCMC to K-562 compared with a normal age-matched control population. However, NCMC levels appear to fluctuate with tumor burden, being highest in patients with large tumor masses and lowest in patients with no clinical evidence of tumor following a successful response to therapy.