The entire DNA sequence of chromosome III of the yeast Saccharomyces cerevisiae has been determined. This is the first complete sequence analysis of an entire chromosome from any organism. The 315-kilobase sequence reveals 182 open reading frames for proteins longer than 100 amino acids, of which 37 correspond to known genes and 29 more show some similarity to sequences in databases. Of 55 new open reading frames analysed by gene disruption, three are essential genes; of 42 non-essential genes that were tested, 14 show some discernible effect on phenotype and the remaining 28 have no overt function.

As resistance to artemisinins (current frontline drugs in malaria treatment) emerges in Southeast Asia, there is an urgent need to identify the genetic determinants and understand the molecular mechanisms underpinning such resistance. Such insights could lead to prospective interventions to contain resistance and prevent the eventual spread to other regions where malaria is endemic. Reduced susceptibility to artemisinin in Southeast Asia has been primarily linked to mutations in the Plasmodium falciparum Kelch-13 gene, which is currently widely recognized as a molecular marker of artemisinin resistance. However, two mutations in a ubiquitin hydrolase, UBP-1, have been previously associated with reduced artemisinin susceptibility in a rodent model of malaria, and some cases of UBP-1 mutation variants associated with artemisinin treatment failure have been reported in Africa and SEA. In this study, we employed CRISPR-Cas9 genome editing and preemptive drug pressures to test these artemisinin susceptibility-associated mutations in UBP-1 in Plasmodium berghei sensitive lines in vivo. Using these approaches, we show that the V2721F UBP-1 mutation results in reduced artemisinin susceptibility, while the V2752F mutation results in resistance to chloroquine (CQ) and moderately impacts tolerance to artemisinins. Genetic reversal of the V2752F mutation restored chloroquine sensitivity in these mutant lines, whereas simultaneous introduction of both mutations could not be achieved and appears to be lethal. Interestingly, these mutations carry a detrimental growth defect, which would possibly explain their lack of expansion in natural infection settings. Our work provides independent experimental evidence on the role of UBP-1 in modulating parasite responses to artemisinin and chloroquine under in vivo conditions.

A number of key risk factors have been identified to be strongly associated with the development of congenital hydrocephalus in an infant. The prevalence of familial patterns of inheritance for congenital hydrocephalus suggests a broader role for genetic factors in the pathogenesis of congenital hydrocephalus.

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Summary. Anxiety levels were studied in 176 women with raised serum α‐fetoprotein levels at 16–18 weeks gestation, at the time they attended a central assessment clinic, and again 2–3 weeks later in those not found to have a fetus with a neural‐tube defect. Methods of imparting information about the serum screening tests and the manner in which a normal amniotic fluid result was conveyed to the patient were also studied. Overall, women attending the clinic for further assessment were extremely anxious, irrespective of the source of their information. Anxiety scores 2–3 weeks after testing were greatly influenced by whether the patient had been given a definite normal result or whether she was told to assume that the result was normal if she did not hear from the clinic. Patients who, after reassessment, did not require amniocentesis had some residual anxiety in spite of verbal reassurance.

The transmission of malaria parasites from vertebrate host to mosquito vector requires a developmental switch in asexually dividing blood-stage parasites to sexual reproduction. In Plasmodium berghei the transcription factor AP2-G is required and sufficient for this switch, but how a particular sex is determined in a haploid parasite remains unknown. Using a global screen of barcoded mutants, we here identify ten genes essential for the formation of either male or female sexual forms and validate their importance for transmission. High-resolution single-cell transcriptomics of wild-type and mutant parasites portrays the developmental bifurcation and reveals a regulatory cascade of putative gene functions in determination and subsequent differentiation of each sex. A male-determining gene with a LOTUS/OST-HTH domain points towards unexpected conservation of molecular mechanisms of gametogenesis in animals and a distantly related eukaryotic parasite.

Summary Intravenous salbutamol, a β‐adrenoceptor stimulant, given to nine patients in normal labour, with continuous monitoring of uterine activity and of the maternal and fetal cardiovascular systems, was shown to decrease uterine activity significantly; maternal and fetal heart rates were significantly increased, and maternal systolic and diastolic arterial pressures were significantly decreased during the infusion, although no treatment had to be discontinued because of these effects. Apart from worsening of low back pain during the infusion in one patient, subjective sideeffects were trivial. With the salbutamol infusion continued at an effective maintenance rate, the cardioselective β‐adrenoceptor blocking drug, practolol, given intravenously, reduced the maternal heart rate (although not significantly) but it did not alter the fetal heart rate; it also appeared to interfere transiently with the inhibiting action of salbutamol on uterine activity, but cervical dilatation was arrested until the salbutamol infusion was discontinued. At least in five patients, labour remained suppressed until oxytocin was infused intravenously.

1 resistance to artemisinin and chloroquine in Plasmodium berghei.