Introgression and disruption of migration routes have shaped the genetic integrity of wildebeest populations.

The blue wildebeest (Connochaetes taurinus) is a keystone species in savanna ecosystems from southern to eastern Africa, and is well known for its spectacular migrations and locally extreme abundance. In contrast, the black wildebeest (C. gnou) is endemic to southern Africa, barely escaped extinction in the 1900s and is feared to be in danger of genetic swamping from the blue wildebeest. Despite the ecological importance of the wildebeest, there is a lack of understanding of how its unique migratory ecology has affected its gene flow, genetic structure and phylogeography. Here, we analyze whole genomes from 121 blue and 22 black wildebeest across the genus' range. We find discrete genetic structure consistent with the morphologically defined subspecies. Unexpectedly, our analyses reveal no signs of recent interspecific admixture, but rather a late Pleistocene introgression of black wildebeest into the southern blue wildebeest populations. Finally, we find that migratory blue wildebeest populations exhibit a combination of long-range panmixia, higher genetic diversity and lower inbreeding levels compared to neighboring populations whose migration has recently been disrupted. These findings provide crucial insights into the evolutionary history of the wildebeest, and tangible genetic evidence for the negative effects of anthropogenic activities on highly migratory ungulates.

Population structure and migration in the Eastern Highlands of Papua New Guinea, a region impacted by the kuru epidemic.

Populations of the Eastern Highlands of Papua New Guinea (EHPNG, area 11,157 km2) lived in relative isolation from the rest of the world until the mid-20th century, and the region contains a wealth of linguistic and cultural diversity. Notably, several populations of EHPNG were devastated by an epidemic prion disease, kuru, which at its peak in the mid-twentieth century led to some villages being almost depleted of adult women. Until now, population genetic analyses to learn about genetic diversity, migration, admixture, and the impact of the kuru epidemic have been restricted to a small number of variants or samples. Here, we present a population genetic analysis of the region based on genome-wide genotype data of 943 individuals from 21 linguistic groups and 68 villages in EHPNG, including 34 villages in the South Fore linguistic group, the group most affected by kuru. We find a striking degree of genetic population structure in the relatively small region (average FST between linguistic groups 0.024). The genetic population structure correlates well with linguistic grouping, with some noticeable exceptions that reflect the clan system of community organization that has historically existed in EHPNG. We also detect the presence of migrant individuals within the EHPNG region and observe a significant excess of females among migrants compared to among non-migrants in areas of high kuru exposure (p = 0.0145, chi-squared test). This likely reflects the continued practice of patrilocality despite documented fears and strains placed on communities as a result of kuru and its associated skew in female incidence.

Giraffe lineages are shaped by major ancient admixture events.

Strong genetic structure has prompted discussion regarding giraffe taxonomy,1,2,3 including a suggestion to split the giraffe into four species: Northern (Giraffa c. camelopardalis), Reticulated (G. c. reticulata), Masai (G. c. tippelskirchi), and Southern giraffes (G. c. giraffa).4,5,6 However, their evolutionary history is not yet fully resolved, as previous studies used a simple bifurcating model and did not explore the presence or extent of gene flow between lineages. We therefore inferred a model that incorporates various evolutionary processes to assess the drivers of contemporary giraffe diversity. We analyzed whole-genome sequencing data from 90 wild giraffes from 29 localities across their current distribution. The most basal divergence was dated to 280 kya. Genetic differentiation, FST, among major lineages ranged between 0.28 and 0.62, and we found significant levels of ancient gene flow between them. In particular, several analyses suggested that the Reticulated lineage evolved through admixture, with almost equal contribution from the Northern lineage and an ancestral lineage related to Masai and Southern giraffes. These new results highlight a scenario of strong differentiation despite gene flow, providing further context for the interpretation of giraffe diversity and the process of speciation in general. They also illustrate that conservation measures need to target various lineages and sublineages and that separate management strategies are needed to conserve giraffe diversity effectively. Given local extinctions and recent dramatic declines in many giraffe populations, this improved understanding of giraffe evolutionary history is relevant for conservation interventions, including reintroductions and reinforcements of existing populations.

Nonlinear topological symmetry protection in a dissipative system.

We investigate experimentally and theoretically a system ruled by an intricate interplay between topology, nonlinearity, and spontaneous symmetry breaking. The experiment is based on a two-mode coherently-driven optical resonator where photons interact through the Kerr nonlinearity. In presence of a phase defect, the modal structure acquires a synthetic Möbius topology enabling the realization of spontaneous symmetry breaking in inherently bias-free conditions without fine tuning of parameters. Rigorous statistical tests confirm the robustness of the underlying symmetry protection, which manifests itself by a periodic alternation of the modes reminiscent of period-doubling. This dynamic also confers long term stability to various localized structures including domain walls, solitons, and breathers. Our findings are supported by an effective Hamiltonian model and have relevance to other systems of interacting bosons and to the Floquet engineering of quantum matter. They could also be beneficial to the implementation of coherent Ising machines.

African bushpigs exhibit porous species boundaries and appeared in Madagascar concurrently with human arrival.

Several African mammals exhibit a phylogeographic pattern where closely related taxa are split between West/Central and East/Southern Africa, but their evolutionary relationships and histories remain controversial. Bushpigs (Potamochoerus larvatus) and red river hogs (P. porcus) are recognised as separate species due to morphological distinctions, a perceived lack of interbreeding at contact, and putatively old divergence times, but historically, they were considered conspecific. Moreover, the presence of Malagasy bushpigs as the sole large terrestrial mammal shared with the African mainland raises intriguing questions about its origin and arrival in Madagascar. Analyses of 67 whole genomes revealed a genetic continuum between the two species, with putative signatures of historical gene flow, variable FST values, and a recent divergence time (<500,000 years). Thus, our study challenges key arguments for splitting Potamochoerus into two species and suggests their speciation might be incomplete. Our findings also indicate that Malagasy bushpigs diverged from southern African populations and underwent a limited bottleneck 1000-5000 years ago, concurrent with human arrival in Madagascar. These results shed light on the evolutionary history of an iconic and widespread African mammal and provide insight into the longstanding biogeographic puzzle surrounding the bushpig's presence in Madagascar.

Population genomics of the muskox' resilience in the near absence of genetic variation.

Genomic studies of species threatened by extinction are providing crucial information about evolutionary mechanisms and genetic consequences of population declines and bottlenecks. However, to understand how species avoid the extinction vortex, insights can be drawn by studying species that thrive despite past declines. Here, we studied the population genomics of the muskox (Ovibos moschatus), an Ice Age relict that was at the brink of extinction for thousands of years at the end of the Pleistocene yet appears to be thriving today. We analysed 108 whole genomes, including present-day individuals representing the current native range of both muskox subspecies, the white-faced and the barren-ground muskox (O. moschatus wardi and O. moschatus moschatus) and a ~21,000-year-old ancient individual from Siberia. We found that the muskox' demographic history was profoundly shaped by past climate changes and post-glacial re-colonizations. In particular, the white-faced muskox has the lowest genome-wide heterozygosity recorded in an ungulate. Yet, there is no evidence of inbreeding depression in native muskox populations. We hypothesize that this can be explained by the effect of long-term gradual population declines that allowed for purging of strongly deleterious mutations. This study provides insights into how species with a history of population bottlenecks, small population sizes and low genetic diversity survive against all odds.

Random number generation using spontaneous symmetry breaking in a Kerr resonator.

We demonstrate an all-optical random number generator based on spontaneous symmetry breaking in a coherently driven Kerr resonator. Random bit sequences are generated by repeatedly tuning a control parameter across a symmetry-breaking bifurcation that enacts random selection between two possible steady-states of the system. Experiments are performed in a fiber ring resonator, where the two symmetry-broken steady-states are associated with orthogonal polarization modes. Detrimental biases due to system asymmetries are suppressed by leveraging a recently discovered self-symmetrization phenomenon that ensures the symmetry-breaking dynamics act as an unbiased coin toss, with a genuinely random selection between the two available steady-states. We optically generate bits at a rate of 3 MHz without post-processing and verify their randomness using the National Institute of Standards and Technology and Dieharder statistical test suites.

Neurodegeneration in a novel invertebrate model system: Failed microtubule-mediated cell adhesion and unraveling of macroglia.

Neurodegenerative diseases are among the main causes of death in the United States, leading to irreversible disintegration of neurons. Despite intense international research efforts, cellular mechanisms that initiate neurodegeneration remain elusive, thus inhibiting the development of effective preventative and early onset medical treatment. To identify underlying cellular mechanisms that initiate neuron degeneration, it is critical to identify histological and cellular hallmarks that can be linked to underlying biochemical processes. Due to the poor tissue preservation of degenerating mammalian brain tissue, our knowledge regarding histopathological hallmarks of early to late degenerative stages is only fragmentary. Here, we introduce a novel model organism to study histological hallmarks of neurodegeneration, the spider Cupiennius salei. We utilized toluidine blue-stained 0.9-µm serial semithin and 50-nm ultrathin sections of young and old spider nervous tissue. Our findings suggest that the initial stages of neurodegeneration in spiders may be triggered by (1) dissociation of neuron- and glia-derived microtubules, and (2) the weakening of microtubule-associated desmosomal junctions that lead to the unraveling of neuron-insulating macroglia, compromising the structural integrity of affected neurons. The involvement of macroglia in the disposal of neuronal debris described here-although different in the proposed transport mechanisms-shows resemblance to the mammalian glymphatic system. We propose that this model system is highly suitable to investigate invertebrate neurodegenerative processes from early onset to scar formation and that this knowledge may be useful for the study of neurodegeneration in mammalian tissue.

Colonialism in South Africa leaves a lasting legacy of reduced genetic diversity in Cape buffalo.

The iconic Cape buffalo has experienced several documented population declines in recent history. These declines have been largely attributed to the late 19th century rinderpest pandemic. However, the effect of the rinderpest pandemic on their genetic diversity remains contentious, and other factors that have potentially affected this diversity include environmental changes during the Pleistocene, range expansions and recent human activity. Motivated by this, we present analyses of whole genome sequencing data from 59 individuals from across the Cape buffalo range to assess present-day levels of genome-wide genetic diversity and what factors have influenced these levels. We found that the Cape buffalo has high average heterozygosity overall (0.40%), with the two southernmost populations having significantly lower heterozygosity levels (0.33% and 0.29%) on par with that of the domesticated water buffalo (0.29%). Interestingly, we found that these lower levels are probably due to recent inbreeding (average fraction of runs of homozygosity 23.7% and 19.9%) rather than factors further back in time during the Pleistocene. Moreover, detailed investigations of recent demographic history show that events across the past three centuries were the main drivers of the exceptional loss of genetic diversity in the southernmost populations, coincident with the onset of colonialism in the southern extreme of the Cape buffalo range. Hence, our results add to the growing body of studies suggesting that multiple recent human-mediated impacts during the colonial period caused massive losses of large mammal abundance in southern Africa.

Compliance in recreational fisheries: Case study of two blue swimmer crab fisheries.

Comparing two Australian regions, Western Australia (WA) and South Australia (SA), this research investigates official noncompliance datasets of recreational blue swimmer crab (Portunus armatus) fishing between 2009 and 2019. These recreational fisheries in both jurisdictions are license-free and therefore participating fisher information is limited. Analyses provide a glimpse at the (noncompliant) fisher population profiles against the application of management strategies. The data provide (1) an evidence-base to optimize regulatory strategies by balancing education and enforcement activities with recreational fisher enjoyment. The results of this research enable application within and beyond these fisheries and jurisdictions; and (2) drawing from the criminology discipline, deterrence theory offers insight to enhance compliance tools. Further, it shows the importance of a multi-disciplinary approach to assessing compliance and identifies some practical approaches to data collection that can be readily undertaken to assist with more detailed analysis and enhance compliance strategies.

High genetic diversity and low differentiation reflect the ecological versatility of the African leopard.

Large carnivores are generally sensitive to ecosystem changes because their specialized diet and position at the top of the trophic pyramid is associated with small population sizes. Accordingly, low genetic diversity at the whole-genome level has been reported for all big cat species, including the widely distributed leopard. However, all previous whole-genome analyses of leopards are based on the Far Eastern Amur leopards that live at the extremity of the species' distribution and therefore are not necessarily representative of the whole species. We sequenced 53 whole genomes of African leopards. Strikingly, we found that the genomic diversity in the African leopard is 2- to 5-fold higher than in other big cats, including the Amur leopard, likely because of an exceptionally high effective population size maintained by the African leopard throughout the Pleistocene. Furthermore, we detected ongoing gene flow and very low population differentiation within African leopards compared with those of other big cats. We corroborated this by showing a complete absence of an otherwise ubiquitous equatorial forest barrier to gene flow. This sets the leopard apart from most other widely distributed large African mammals, including lions. These results revise our understanding of trophic sensitivity and highlight the remarkable resilience of the African leopard, likely because of its extraordinary habitat versatility and broad dietary niche.

Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study.

BACKGROUND: Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci have been confirmed. We aimed to discover new genetic risk factors for sCJD, and their causal mechanisms. METHODS: We did a genome-wide association study of sCJD in European ancestry populations (patients diagnosed with probable or definite sCJD identified at national CJD referral centres) with a two-stage study design using genotyping arrays and exome sequencing. Conditional, transcriptional, and histological analyses of implicated genes and proteins in brain tissues, and tests of the effects of risk variants on clinical phenotypes, were done using deep longitudinal clinical cohort data. Control data from healthy individuals were obtained from publicly available datasets matched for country. FINDINGS: Samples from 5208 cases were obtained between 1990 and 2014. We found 41 genome-wide significant single nucleotide polymorphisms (SNPs) and independently replicated findings at three loci associated with sCJD risk; within PRNP (rs1799990; additive model odds ratio [OR] 1·23 [95% CI 1·17-1·30], p=2·68 × 10-15; heterozygous model p=1·01 × 10-135), STX6 (rs3747957; OR 1·16 [1·10-1·22], p=9·74 × 10-9), and GAL3ST1 (rs2267161; OR 1·18 [1·12-1·25], p=8·60 × 10-10). Follow-up analyses showed that associations at PRNP and GAL3ST1 are likely to be caused by common variants that alter the protein sequence, whereas risk variants in STX6 are associated with increased expression of the major transcripts in disease-relevant brain regions. INTERPRETATION: We present, to our knowledge, the first evidence of statistically robust genetic associations in sporadic human prion disease that implicate intracellular trafficking and sphingolipid metabolism as molecular causal mechanisms. Risk SNPs in STX6 are shared with progressive supranuclear palsy, a neurodegenerative disease associated with misfolding of protein tau, indicating that sCJD might share the same causal mechanisms as prion-like disorders. FUNDING: Medical Research Council and the UK National Institute of Health Research in part through the Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust.

The association between hyponatraemia and long-term functional outcome in patients with aneurysmal subarachnoid haemorrhage: A single centre prospective cohort study.

To assess the association between hyponatraemia and long-term functional outcome and other relevant outcomes in patients with aneurysmal subarachnoid haemorrhage (aSAH) we conducted a prospective cohort study in a Neurosciences Intensive Care Unit (ICU) in Sydney, Australia. The primary exposure variable was hyponatraemia (Na+ <135 mmol/L). The primary outcome was favourable outcome, a score of 5-8 on the extended Glasgow Outcome Score (GOSe) at 12 months. We also measured mortality, the incidence of delayed cerebral ischaemia (DCI) and cerebral arterial vasospasm and duration of ICU and hospital admission. There were 200 participants, 111 (56%) developed hyponatraemia. Hyponatraemia was not associated with favourable outcome at 12 months (unadjusted odds ratio [OR] OR 1.31, 95% confidence interval [CI] 0.65-2.65, p = 0.56). The result was similar after adjustment for baseline covariates (adjusted OR 0.60, 95% CI 0.16-1.99, p = 0.43). There was no association between hyponatraemia and the incidence of DCI (OR 0.95, 95% CI 0.46 to 2.0, p > 0.99) nor cerebral arterial vasospasm (OR 1.4, 95% CI 0.8 to 2.5, p = 0.27). Those who developed hyponatraemia had a longer median duration of ICU admission (17 days, interquartile range [IQR] 12 to 20, compared to 13 days, IQR 8-21, p = 0.02) and longer median duration of hospital admission (24 days, IQR 21-30, compared to 22 days IQR 14-31, p = 0.05). While hyponatraemia is common following aSAH, it is not associated with worse long-term functional outcome, increased rate of DCI, nor cerebral arterial vasospasm. Hyponatraemia in patients with aSAH was associated with longer duration of ICU and hospital admission.

Paediatric surgical services in remote northern Australia: an integrated model of care.

BACKGROUND: Surgical services for children in the Northern Territory of Australia are routinely performed by general surgeons with specific paediatric training, supported by paediatric surgeons. In Australasia, indications for appropriate transfer of elective routine surgery in children to tertiary paediatric surgical centres have been contentious. To transfer all elective paediatric cases from rural locations would have significant social and financial consequences for families and the health system. This study reviews clinical outcomes for elective surgery for two common conditions managed by an integrated service of general surgeons and visiting paediatric surgeons, and compares them with published outcomes from paediatric centres. METHOD: A retrospective audit of children undergoing orchidopexy under the age of 5 years or inguinal herniotomy under the age of 1 year at the Royal Darwin Hospital and Darwin Private Hospital between January 2005 and 2016 was conducted. RESULTS: During the study period, 66 boys underwent 80 orchidopexies at a mean age of 22.3 months (±20.4 SD). A recurrence rate of 5.5%, severe atrophy rate of 1.3% and total atrophy rate of 5.5% were achieved. Sixty-three children underwent 65 inguinal herniotomies at a mean age of 2.5 months (±4.2). A testicular maldescention and atrophy rate of 1.8% and recurrence rate of 0% was achieved. CONCLUSION: Children managed with this model of care had complication rates equivalent to or slightly higher than published gold standards. Considering the family disruption, cultural, financial implications and threat to compliance that transfer across vast distances entails, this model provides acceptable outcomes.

Iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent peritoneal metastases.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) achieves disease control within the peritoneum but recurrences occur. This study examines the outcomes of iterative CRS (iCRS) HIPEC for treatment of recurrent peritoneal metastases. METHODS: Patients who underwent iCRS in a single tertiary referral center were identified from a prospective database. Safety analysis was performed and clinicopathological variables were analyzed to assess factors predictive of major morbidity and survival. RESULTS: The demographics of patients who underwent primary cytoreductive surgery (pCRS) (n = 466) and iCRS (n = 79) were balanced between groups. pCRS was shown to require more blood transfusion (P = 0.019) and albumin use (P = 0.013). The mortality and major complication rates were comparable (1.2% vs. 0%; P = 0.600, and 42% vs. 41%; P = 0.806). Residual pneumothorax occurred more frequently after pCRS (12% vs. 4%; P = 0.030). Factors associated with major complications after iCRS include use of HIPEC (P = 0.042) and length of hospital stay (P = 0.024). The overall median survival was 48 months and 5-year survival was 34%. By cancer type, the 3-year survival was 0%, 74%, 80%, and 72% for colorectal, appendiceal pseudomyxoma, peritoneal mesothelioma, and appendix cancer, respectively. Independent predictors of survival include age (P = 0.049), interval between pCRS and iCRS (P = 0.008), small bowel resection (P < 0.001), and use of HIPEC (P = 0.005). CONCLUSION: Iterative CRS achieved further peritoneal disease control without adverse effects on morbidity. Patients with appendiceal tumors and peritoneal mesothelioma appear to benefit most after iCRS. Intraoperative HIPEC remains important in the repetoire of managing these patients.