A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16

Adult polycystic kidney disease (APCKD) is a common and often lethal multi-organ disease with an autosomal dominant pattern of inheritance; approximately 1 in 1,000 people carry the mutant gene. The major pathological abnormality is the development and progressive enlargement of cysts in several organs including the liver, pancreas and spleen as well as the kidneys. The basic biochemical defect which leads to the formation of cysts remains unknown. Cyst development, which is not retarded by any known therapy, leads to irreversible renal failure and death at a mean age of 51 unless dialysis or transplantation are used. Patients with the disease account for 9% of chronic dialysis requirement. The first symptoms tend to occur in the fourth decade, after most patients have reproduced. Presymptomatic diagnosis depends on the ultrasonographic detection of cysts, but exclusion cannot be achieved by this means; 34% of at-risk patients in the second decade and 14% in the third will go on to develop cysts after negative diagnosis. The low sensitivity of diagnostic techniques in this critical age-range imposes severe limitations on genetic counselling and the condition cannot be identified prenatally. Hence we have searched for a linkage marker for APCKD; we show here that the APCKD locus is closely linked to the alpha-globin locus on the short arm of chromosome 16 (zeta = 25.85, theta = 0.05).     

Negative epistasis between the malaria-protective effects of alpha+-thalassemia and the sickle cell trait

The hemoglobinopathies, disorders of hemoglobin structure and production, protect against death from malaria. In sub-Saharan Africa, two such conditions occur at particularly high frequencies: presence of the structural variant hemoglobin S and alpha(+)-thalassemia, a condition characterized by reduced production of the normal alpha-globin component of hemoglobin. Individually, each is protective against severe Plasmodium falciparum malaria, but little is known about their malaria-protective effects when inherited in combination. We investigated this question by studying a population on the coast of Kenya and found that the protection afforded by each condition inherited alone was lost when the two conditions were inherited together, to such a degree that the incidence of both uncomplicated and severe P. falciparum malaria was close to baseline in children heterozygous with respect to the mutation underlying the hemoglobin S variant and homozygous with respect to the mutation underlying alpha(+)-thalassemia. Negative epistasis could explain the failure of alpha(+)-thalassemia to reach fixation in any population in sub-Saharan Africa.     

On the status of the geodesic principle in Newtonian and relativistic physics

A theorem due to Geroch and Jang (1975) provides a sense in which the geodesic principle has the status of a theorem in General Relativity. I have recently shown that a similar theorem holds in the context of geometrized Newtonian gravitation (Newton–Cartan theory) (Weatherall, J.O., 2011). Here I compare the interpretations of these two theorems. I argue that despite some apparent differences between the theorems, the status of the geodesic principle in geometrized Newtonian gravitation is, mutatis mutandis, strikingly similar to the relativistic case.     

Nanosecond radio bursts from strong plasma turbulence in the Crab pulsar

The Crab pulsar was discovered by the occasional exceptionally bright radio pulses it emits, subsequently dubbed 'giant' pulses. Only two other pulsars are known to emit giant pulses. There is no satisfactory explanation for the occurrence of giant pulses, nor is there a complete theory of the pulsar emission mechanism in general. Competing models for the radio emission mechanism can be distinguished by the temporal structure of their coherent emission. Here we report the discovery of isolated, highly polarized, two-nanosecond subpulses within the giant radio pulses from the Crab pulsar. The plasma structures responsible for these emissions must be smaller than one metre in size, making them by far the smallest objects ever detected and resolved outside the Solar System, and the brightest transient radio sources in the sky. Only one of the current models--the collapse of plasma-turbulent wave packets in the pulsar magnetosphere--can account for the nanopulses we observe.