semans's blog

Given that kuru was historically and geographically constrained and that there have been no cases of the disease since 2005, it is unsurprising that recent and future research into the disease has been limited. The most recent findings relating to kuru were reported by Mead et al. in their paper on genetic immunity to kuru in the Fore people (2009). Now that the disease is extinct, interest in the disease has faltered, only exacerbated by the fact that there are virtually no more intact kuru infected brains available for study (Hainfellner et al., 1997). Thus, although kuru has provided great insight into prion mediated neurodegeneration and was fundamental to the development of prion theory, it is no longer the object of much scientific research.

In summary, kuru is a neurodegenerative disorder that is historically constrained to the mid-20th century and geographically limited to the Fore speaking tribes of Papua New Guinea. It originated by spontaneous CJD in one individual and spread to other individuals via these tribes’ cannibalistic mortuary rites. Its root biological cause is prions, that produce neurotoxic compounds as they aggregate into undegradable deposits found most prominently the cerebral cortex, the cingulate cortex, the striatum, the thalamus, and the cerebellar cortex. Thus far, kuru can only be prevented by genetic immunity via mutations in the PrP gene. Otherwise, there is no cure for kuru and death is its only prognosis. 

Chirp structure and EOD frequency are sexually dimorphic to different extents across wave-type species. In Apteronotids, males often have lower EOD frequency than females but EOD frequency chirping can be sexually dimorphic in a number of different ways (Smith 2013, 2422; Ho et al. 2013, 335; Ho et al. 2010, 1050). For example, A. albifrons males have lower EOD frequencies than females while A. leptorhynchus males have a higher EOD frequency than females (Smith 2013, 2422). Additionally, in A. leptorhynchus, males chirp more than females but their chirp complexity is similar while in A. bonapartii and A. devenanzii chirp complexity and not chirp rate is higher in males than in females (Smith 2013, 2428; Ho et al. 2010, 1059). Another Apteronotid, Sternarchogiton nattereri, shows no sexual dimorphism, as males and females show no discernible difference in EOD frequency, chirp rate, or chirp form (Ho et al. 2013,337). Instead, S. nattereri shows differences in EOD frequency that are dependent on male morphology, as toothed males show higher EOD frequency than toothless males (Fernandes et al. 2010, 660). In the wave-type Gymnotiform Gymnotus omarorum, and unlike in many of the aforementioned wave-type Apteronotids, electric signalling is sexually monomorphic (Batista et al. 2012, 398). Such sexually monomorphic electrocommunicative behaviour has also been observed in other non-Apteronotid genera such Eigenmannia and Sternopygus (Smith 2013, 2422).

 In summary, although the last decade has produced many studies on social electrocommunication in weakly electric fish, they have been biased towards proximate research and to some extent wave-type species. Species recognition in the wave-type fish A. leptorhynchus is mediated by stereotyped EOD frequencies and in the pulse-type fish. M. rume it is determined by a species-specific IDI (Fugère & Krahe 2010, 213; Dunlap et al. 2010, 2234; Worm et al. 2018, 1). JAR seems to be unique to wave-type species and has been hypothesized to have an intrasocial function in Apteronidae, Eigenmannia, and Dystocyclus, but seems absent from Sternopygus (Worm et al. 2018, 1; Stamper et al. 2010, 368). Ritualised aggression in weakly electric fish is often negotiated via modulated EOD frequencies, EOD lengths, and IDI patterns that signal the dominance of one fish over another, and in the males of some species, dominance strongly correlates with levels of 11-ketotestosterone (Gebhardt et al. 2012, 623; Fugère et al. 2011, 197; Salazar & Stoddard 2009, 399; Cuddy et al. 2012, 4; Raab et al. 2019, 1). Sexual dimorphism of EODs is evolutionarily labile, as A. leptorhynchus shows sexual dimorphism in EOD frequency and chirping while many other wave-type genera are sexually monomorphic (Smith 2013, 2428; Batista et al. 2012, 398). S. nattereri is a unique case where electrocommunication is sexually monomorphic but different male morphs vary in their EOD frequencies (Ho et al. 2013,337; Fernandes et al. 2010, 660). Lastly, pulse-type fish of the Marcusenius genus also show differences in sexual dimorphism, as M. pongolensis males show a life-long increase in their EOD length while male M. altisambesi only show increased EOD length during the breeding season (Machnik et al. 2010, 699). Overall, these studies show that weakly electric fish use electrocommunication in a variety of contexts and explore how electrocommunication takes place but explanations for its evolution remain largely in the hypothetical realm. Answering ultimate questions about electrocommunication would be facilitated by studies into: (1) how differences in selection pressures have affected species differences in electrocommunication, (2) the evolutionary history of electrocommunication in Gymnotiformes and Mormyriformes to understand how these groups diverged and became segregated to South America and Africa respectively, (3) the environmental and evolutionary factors that contribute to sexually dimorphic electrocommunication.

Chirp structure and EOD frequency differs across wave-type fish and can be sexually dimorphic, though to different extents. In Apteronotids, EOD frequency - males often have lower EOD frequency than females - and chirping can be sexually dimorphic, but appears in a number of different ways (Smith 2013, 2422; Ho et al. 2013, 335; Ho et al. 2010, 1050). For example, A. albifrons males have lower EOD frequencies than females while A. leptorhynchus males have a higher EOD frequency than females (Smith 2013, 2422). Additionally, in A. leptorhynchus, males chirp more than females and in A. bonapartii and A. devenanzii chirp complexity is higher in males than in females (Smith 2013, 2428; Ho et al. 2010, 1059). However, another Apteronotid Sternarchogiton nattereri shows no sexual dimorphism, as males and females show no discernible difference in EOD frequency, chirp rate, and chirp form (Ho et al. 2013,337). Instead, S. nattereri shows differences in EOD frequency that are dependent on male morphology, with toothed males showing higher EOD frequency than toothless males (Fernandes et al. 2010, 660). In the wave-type Gymnotiform Gymnotus omarorum, and unlike in many of the aforementioned Apteronotids, electric signalling is sexually monomorphic (Batista et al. 2012, 398). Sexually monomorphic electrocommunicative behaviour has also been observed in other non-Apteronotid genera such Eigenmannia and Sternopygus (Smith 2013, 2422).

One important use of electrocommunication in weakly electric fish species is conspecific and heterospecific recognition. The use of electric signals for this purpose has been demonstrated in both wave-type and pulse-type fish (Fugère & Krahe 2010, 213; Dunlap et al. 2010, 213; Worm et al. 2018, 1). Counterintuitively, some weakly electric fish preferentially avoid conspecific signals, and this has been attributed to differences in their jamming avoidance response (JAR) (Stamper et al. 2010, 368). Interestingly, it has been hypothesized that JAR doesn’t just serve to avoid interference among fish living in a group, but also as a means of intragroup communication (Stamper et al. 2010, 376; Petzold et al. 2018, 1). 

Species recognition has been demonstrated in the wave-type brown ghost knifefish, Apteronotus leptorhynchus (Fugère & Krahe 2010, 213; Dunlap et al. 2010, 2234). Like other wave-type fish, A. leptorhynchus modulates the frequency and amplitude of its EOD, to produce communication signals generally referred to as “chirps”, “rises”, and “interruptions” (Fugère & Krahe 2010, 213). It has been shown that the waveform of the electrical stimuli A. leptorhynchus encounters does not affect its chirping or approach behaviour whereas frequency changes have a strong effect on chirping and approach behaviour (Fugère & Krahe 2010, 231). This has been corroborated by another study, whose findings show that A. leptorhynchus chirp rate changes when the fish is presented with electrical stimuli that have different frequencies (Dunlap et al. 2010, 2234). Thus, current findings suggest that A. leptorhynchus uses changes in frequency and not waveform to recognise conspecifics (Fugère & Krahe 2010, 234). It has also been shown that A. leptorhynchus can distinguish between conspecifics and heterospecifics, chirping at higher rates in response to conspecifics and at lower rates in response to heterospecifics (Dunlap et al. 2010, 2241). However, there lacks research into whether or not heterospecific type chirp response has any communicative value in A. leptorhynchus (Dunlap et al. 2010, 2241). In addition, the evolutionary origins and adaptive value of this type of electrocommunication in A. leptorhynchus have yet to be discovered.

Only relatively recently, it was shown that a pulse-type fish, Mormyrus rume proboscirostris (M. rume), also uses electrical signaling for species recognition (Worm et al. 2018, 1). In the absence of both vision and the lateral line system, M. rume can rely solely on its electrocommunication system to track and match a source of conspecific electrical signals (Worm et al. 2018, 1). M. rume recognise each other via stereotyped inter-discharge intervals (IDIs) that consist of a short sequence of double-pulses, synchronized at approximately the same frequency as the conspecific signal they receive (Worm et al. 2018, 4). Additionally, and as opposed to A. leptorhynchus behaviour, it was shown that M. rume uses conspecific electrical signals to orient itself spatially, as observed by its following behaviour when presented with a moving source of conspecific signals (Worm et al. 2018, 10).

Weakly electric fish are a subset of electric fish species that typically generate electric discharges under one volt (University of Virginia, n.d.). Both weakly and strongly electric fish have an electric organ in their tail composed of electrocytes that they can excite to cause electrical organ discharges (EODs), which they sense via electroreceptors embedded in their skin (University of Virginia, n.d.). Through this mechanism, weakly electric fish can electrolocate and electrocommunicate (Worm et al. 2018, 221). During electrocommunication, weakly electric fish encode information in their electrical discharges to transmit to each other information about species, age, gender, identity, and motivation (Zakon & Smith 2009, 611). Weakly electric fish species fall into two types: pulse-type fish which produce short, intermittent pulses of electricity and wave-type fish wich generate continuous A.C. electricity (University of Virginia, n.d.). This review aims to cover the last decade’s research into social electrocommunication in weakly electric fishes including: species recognition, jamming avoidance response, dominance, competition, and sexual dimorphism. Although there has been much research into the electrocommunication behaviours of weakly electric fish, it has by and large been observational research focused on proximate questions. As such, there is a lack of research into important ultimate questions concerning electrocommunication. Ultimate avenues of inquiry in future research may provide insight into why electrocommunication first developed, and why weakly electric fish species are confined to the South American and African continents (Moller 1995, 583). Studying the evolutionary and adaptive aspects of electrocommunication might be a critical step in elucidating important evolutionary relationships in freshwater fishes. 

The presymptomatic phase of kuru lasts, on average, 10 to 13 years but incubation time can range from 5 years to 50 years (Collinge et al., 2008). Mean clinical duration of the disease is 12 months with a range of 3 months to 2 years (Collinge et al., 2008). Kuru infection presents itself in three progressive stages: ambulatory, sedentary, and terminal (Alpers, 2005). The primary physical symptom of the disease, cerebellar ataxia, worsens as the disease advances through these three stages(Gajdusek, 1957). In the ambulatory phase, patients demonstrate a loss of muscular coordination though they are still capable of speaking and moving around (Gajdusek, 1957). In the sedentary stage, infected individuals show stronger ataxia that manifests as major dysarthria, frequent, excessive bursts of laughter and the impossibility of unassisted movement (Gajdusek, 1957). At the terminal stage, infected individuals can no longer sit without support, the ability to speak is lost, urinary and fecal incontinence is common, dysphagia begins, and many develop ulcerated wounds that are prone to infection (Gajdusek, 1957). Death occurs shortly thereafter either due to wound infection or terminal static bronchopneumonia (Gajdusek, 1957).

The presymptomatic phase of kuru lasts, on average, 10 to 13 years but incubation time can range from 5 years to 50 years (Collinge et al., 2008). The mean clinical duration of the disease is 12 months but may be as short as 3 months, as long as 2 years, or even longer in some atypical cases (Collinge et al., 2008). Kuru infection progresses through three general stages: ambulatory, sedentary, and terminal (Alpers, 2005). Throughout all of these stages, the primary physiological symptom of the disease is progressive cerebellar ataxia (Gajdusek, 1957). In the ambulatory stage, patients demonstrate involuntary tremors, and a lack of coordination, though they are still capable of speaking and moving themselves around (Gajdusek, 1957). In the sedentary stage, an infected individual shows strong ataxia, they cannot move around without assistance, show major dysarthria, and are prone to excessive bursts of laughter (Gajdusek, 1957). At the terminal stage, infected individuals can no longer sit without support, speech is completely lost, urinary and fecal incontinence appear, dysphagia occurs and eventually, many develop ulcerated wounds that are prone to infection (Gajdusek, 1957). Death occurs shortly thereafter either due to wound infection or terminal static bronchopneumonia (Gajdusek, 1957). 

At the neuropathological level, kuru shows similar features to other diseases caused by prions. PrPSC accumulates in grey matter regions throughout the cerebrum, cerebellum, brainstem, and spinal cord, leading to an atrophied brain overall (Hainfellner et al., 1997). PrPSC deposits in two ways: fine, granular deposits that occur perineuronally and periaxonally, and in dense plates with a homogeneous centre surrounded by radiating spikes (Hainfellner et al., 1997). Though PrPSC aggregates resist proteolysis, they are relatively inert. The danger comes as they self-propagate because they create a byproduct called PrPL that is neurotoxic and is directly responsible for neurodegeneration (Collinge & Clarke, 2007). This neurodegeneration presents itself, in part, as fibrillary astrogliosis most apparent in the parasagittal and interhemispheric areas of the frontal, central, and parietal cortex, as well as the cingulate cortex, striatum, and thalamus (Hainfellner et al., 1997). Loss of neurons due to PrPSC accumulation is most prominent in the: dorsomedial frontal cortex, dorsomedial central cortex, pre/parasubiculum of the hippocampus, striatum, thalamus, and inferior olivary nuclei of the medulla (Hainfellner et al., 1997). Though less severely, some PrPSC plates introgress into the white matter of both the cerebrum and the cerebellum (Hainfellner et al., 1997). The brainstem suffers from some neurodegeneration and astrogliosis caused by periaxonal and perineuronal PrPSC deposits rather than plaques (Hainfellner et al., 1997). Lastly, there are accentuated periaxonal and perineuronal PrPSC aggregates in the substantia gelatinosa of the spinal cord (Hainfellner et al., 1997).

    First documented in the early 1950s, Kuru is a rare and incurable disease that was common to the Fore people of Papua New Guinea. It was the first chronic degenerative disorder in humans to be shown to be transmissible and paved the way for the discovery of prions, an entirely new type of disease vector. This review aims to provide a short overview of the history, demographics, causes, symptoms, and neuropathology of kuru and how it has influenced research into other neurological disorders.

    Kuru is a rare disease, and virtually all cases of the disease have been documented in the tribes inhabiting a subregion of Papua New Guinea. At that, less than 3000 cases were ever documented (Alpers, 2007). In 1957, there were 200 deaths due to kuru reported in the Fore population, and by 2005 only 1 death due to kuru was reported in the population, after which no more kuru-related deaths were reported (Alpers, 2007). Kuru first came under study in 1957 - when Charles Pfarr reported that it had become an epidemic in the Fore people - by a virologist named Daniel Carleton Gajdusek (Alpers, 2007). Gajdusek spent two years in Papua New Guinea examining the disease, after which he performed experiments on chimpanzees (Gajdusek, 1957). In 1960, shortly after his reports about the fact that cannibalism was the most likely cause of the disease, the practice was banned, but research into the disease continued (Alpers, 2007). In his experiments, Gajdusek demonstrated that kuru was transmissible and could cross the human-primate species barrier which he attributed to some unknown disease factor that came from the brain matter of infected humans (Gajdusek, 1966). Prions as the root cause of kuru came later, catalysed by E. J. Field’s work comparing kuru to scrapie and multiple sclerosis and his observation that molecular aggregation was critical to the infection process (Field, 1967).

Additionally, the results show that all of the insects become active beyond 20°C. Against the null hypothesis that the insects will show a mean activity count of 10, a T-test generates a p-value of 0.096, which is above 0.05 and therefore not statistically significant. Thus, these results imply that O. fasciatus is at its most active at and above 20°C, which is 5°C above the average daytime temperature in Massachusetts.

There are a number of plausible explanations for these results. Firstly, O. fasciatus covers a wide geographical range, from southern Canada to Costa Rica. Populations of O. fasciatus therefore inhabit different environments and different temperature ranges, and it may simply be that the milkweed bugs we used came from a population that inhabits a warmer climate. Therefore, the insects wouldn’t show the most activity in the Massachusetts average daytime range of 10-20°C but rather at higher temperatures above 20°C.

Alternatively, it may be that O. fasciatus needs a continuous source of food to maintain its body temperature at levels that promote activity and that only under higher heat conditions does its body temperature rise enough for it to become active. Given that the insects were starved 12 hours prior, it may be that they did not have the energy reserves or the necessary metabolites to heat themselves. Therein, when the ambient temperature was raised to 20°C above average daytime temperature, their bodies warmed up to a temperature that promoted activity, one they couldn’t reach due to a lack of energy. The primary confounding factor of this explanation being that they were provided with food during the temperature switching portion of the experiment, and yet none of the insects were seen to forage. However, this effect may have been due to the insects being put into new temperature and visual conditions during the temperature switch, thus motivating them to escape from the arena rather than search for food.

      In summary, O. fasciatus activity is positively linearly correlated with temperature and is highest above 20°C. The data do not corroborate the hypothesis that the insects are most active at an intermediate temperature window of 10-20°C. Based on these results it may be the case that the level of O. fasciatus activity depends on its access to food, as it may need energy reserves to raise body temperature above daytime temperatures in Massachusetts in order to remain active during the day. Further research into O. fasciatus thermoregulation and potential life characteristic divergence among geographically distant O. fasciatus populations is necessary in order to elucidate the reasons behind these results.