Study of Plasmodium falciparum DHHC palmitoyl transferases identifies a role for PfDHHC9 in gametocytogenesis

Palmitoylation is the post‐translational reversible addition of the acyl moiety, palmitate, to cysteine residues of proteins and is involved in regulating protein trafficking, localization, stability and function. The Aspartate‐Histidine‐Histidine‐Cysteine (DHHC) protein family, named for their highly conserved DHHC signature motif, is thought to be responsible for catalysing protein palmitoylation. Palmitoylation is widespread in all eukaryotes, including the malaria parasite, Plasmodium falciparum, where over 400 palmitoylated proteins are present in the asexual intraerythrocytic schizont stage parasites, including proteins involved in key aspects of parasite maturation and development. The P. falciparum genome includes 12 proteins containing the conserved DHHC motif. In this study, we adapted a palmitoyl‐transferase activity assay for use with P. falciparum proteins and demonstrated for the first time that P. falciparum DHHC proteins are responsible for the palmitoylation of P. falciparum substrates. This assay also reveals that multiple DHHCs are capable of palmitoylating the same substrate, indicating functional redundancy at least in vitro. To test whether functional redundancy also exists in vivo, we investigated the endogenous localization and essentiality of a subset of schizont‐expressed PfDHHC proteins. Individual PfDHHC proteins localized to distinct organelles, including parasite‐specific organelles such as the rhoptries and inner membrane complex. Knock‐out studies identified individual DHHCs that may be essential for blood‐stage growth and others that were functionally redundant in the blood stages but may have functions in other stages of parasite development. Supporting this hypothesis, disruption of PfDHHC9 had no effect on blood‐stage growth but reduced the formation of gametocytes, suggesting that this protein could be exploited as a transmission‐blocking target. The localization and stage‐specific expression of the DHHC proteins may be important for regulating their substrate specificity and thus may provide a path for inhibitor development.     

A comparative study of the molecular structures of the plasma membranes and the smooth and the rough endoplasmic-reticulum membranes from rat liver

Plasma-membrane as well as smooth-, rough- and degranulated-endoplasmic-reticulum-membrane fractions were isolated from the microsomal pellet of rat liver. The purity of these fractions, as determined by marker-enzyme activities, electron microscopy, cholesterol content and RNA content, was found to be adequate for a comparative structural study. Major differences in lipid and protein composition were found to exist between the plasma membrane and the endoplasmic reticulum, but not between the smooth and the rough fractions of the endoplasmic reticulum. Differences in the location of membrane protein thiol groups and the mobility of the membrane phospholipids were observed between the plasma membranes and the endoplasmic reticulum, and these could be explained by differences in protein and lipid composition. However, by employing fluorescence and spin-labelling techniques structural changes were also observed between the smooth and the rough endoplasmic-reticulum fractions. These results suggest that the structural heterogeneity existing between the two latter membrane fractions occurs near or on their membrane surfaces and is not due to the greater number of ribosomes bound to the rough endoplasmic-reticulum fraction.     

Insulin-like immunoreactivity in the monkey spinal cord.

Insulin-like immunoreactive neurons were localized in the cervical, thoracic, lumbar and sacral segments of the monkey spinal cord. Both dorsal and ventral horn cells were labelled. Insulin-like reaction product was localized in the cell nucleus and cytoplasm. Both inner and outer nuclear membranes were labelled. Reaction product appeared to be scattered throughout the nucleoplasm but not within the nucleolus. In the cytoplasm, labelling was mainly localized in the cisternae of rER and saccules of Golgi apparatus. Both proximal and distal dendrites were labelled, the reaction product was closely associated with the parallel arrays of neurotubules. Most of the distal dendrites were postsynaptic to non-labelled axon terminals; however, some were postsynaptic to lightly labelled axon terminals. A labelled dendrite often formed the central element of a synaptic glomerulus with several nonlabelled axon terminals. It is hypothesized that insulin-like substance(s) may be modulating nuclear activities as well as neurotransmission at the synapse.     

Mytella strigata (Bivalvia: Mytilidae): an alien mussel recently introduced to Singapore and spreading rapidly

The American brackish-water mussel Mytella strigata is reported from Singapore for the first time. In 2016 a survey of intertidal hard structures in the Johor Straits revealed its almost ubiquitous presence in high mean densities, up to 124?±?32 individuals 25?cm^?2 along the shoreline. Subtidal nets employed by floating fish farms were also fouled with this species. Densities exceeding 10,000 individuals 100?cm^?2 were observed, to the exclusion of its relative Perna viridis, the Asian green mussel. Size-frequency analyses of shells indicated the presence of both juveniles and adults. Juveniles have an extremely variable shell surface pigmentation. The adults, reaching 5?cm in shell length, generally have a thick dark greenish brown to almost black periostracum, but bright green and olive green individuals, some with distinctive brown streaks, have also been observed. However, sequences of the mitochondrial COI gene were consistent with mussels from Brazil, Colombia and Ecuador, where they are natively distributed, while shells were reconcilable with type material. The species may have been transported in ballast water and/or with fouling directly from its native provinces, or spread from the Philippines where there are already established populations of M. strigata, possibly since the nineteenth century.     

On an erroneous view of fluxional behaviour of [Fe3(CO)12]

The idea that the mechanism of the very low energy fluxional behaviour of [Fe₃(CO)₁₂] may be based on the movement of the ligand icosahedron about the central Fe₃ triangle which corresponds to a rotational symmetry operation of the CO ligand icosahedron is discussed and rejected.     

Intestinal candidiasis. A clinical report and comments about this opportunistic pathology

An eight-years-old girl, who presented with recurrent upper respiratory tract infections, was treated with broad-spectrum antibiotics. Afterward she presented with intestinal candidiasis. The isolated species was identified as Candida albicans by differential tests. Treatment given was with 500,000 IU of oral nystatin every 8 hours for 10 days and intestinal normal microbiota restoratives. Evolution has been satisfactory, although concomitantly type A hepatitis developed. Rest and a soft diet were recommended. The child is now perfectly healthy with normal liver function tests. Conclusion: Prolonged treatments with broad-spectrum antibiotics destroyed the indigenous intestinal microbiota, which provoked intestinal C. Albicans proliferation and adversely affected the immunological system of the patient, thus facilitating the establishment of a viral infection.This revised version was published online in October 2005 with corrections to the Cover Date.