In Silico Assessment of LIR Motif-Containing Proteins Binding to ATG8-Family Proteins.

Selective autophagic degradation of cellular components has been shown to be mediated by the interaction of LIR motif-containing proteins with ATG8-family proteins. Here, we present a detailed methodology for the in silico evaluation of potential binding between LIR motif-containing proteins and ATG8-family proteins. We visualize AlphaFold-predicted protein complexes using PyMOL to assess potential interactions, providing an effective computational tool for this purpose.

Ancient genomes reveal insights into ritual life at Chichén Itzá.

The ancient city of Chichén Itzá in Yucatán, Mexico, was one of the largest and most influential Maya settlements during the Late and Terminal Classic periods (AD 600-1000) and it remains one of the most intensively studied archaeological sites in Mesoamerica. However, many questions about the social and cultural use of its ceremonial spaces, as well as its population's genetic ties to other Mesoamerican groups, remain unanswered. Here we present genome-wide data obtained from 64 subadult individuals dating to around AD 500-900 that were found in a subterranean mass burial near the Sacred Cenote (sinkhole) in the ceremonial centre of Chichén Itzá.

Extreme mortality during a historical measles outbreak on Rotuma is consistent with measles immunosuppression.

Until the early twentieth century, populations on many Pacific Islands had never experienced measles. As travel to the Pacific Islands by Europeans became more common, the arrival of measles and other pathogens had devastating consequences. In 1911, Rotuma in Fiji was hit by a measles epidemic, which killed 13% of the island population.

The impacts of SARS-CoV-2 vaccine dose separation and targeting on the COVID-19 epidemic in England.

In late 2020, the JCVI (the Joint Committee on Vaccination and Immunisation, which provides advice to the Department of Health and Social Care, England) made two important recommendations for the initial roll-out of the COVID-19 vaccine. The first was that vaccines should be targeted to older and vulnerable people, with the aim of maximally preventing disease rather than infection. The second was to increase the interval between first and second doses from 3 to 12 weeks.

The erythrocyte membrane properties of beta thalassaemia heterozygotes and their consequences for Plasmodium falciparum invasion.

Malaria parasites such as Plasmodium falciparum have exerted formidable selective pressures on the human genome. Of the human genetic variants associated with malaria protection, beta thalassaemia (a haemoglobinopathy) was the earliest to be associated with malaria prevalence. However, the malaria protective properties of beta thalassaemic erythrocytes remain unclear.

The impact of school reopening on the spread of COVID-19 in England.

By mid-May 2020, cases of COVID-19 in the UK had been declining for over a month; a multi-phase emergence from lockdown was planned, including a scheduled partial reopening of schools on 1 June 2020. Although evidence suggests that children generally display mild symptoms, the size of the school-age population means the total impact of reopening schools is unclear. Here, we present work from mid-May 2020 that focused on the imminent opening of schools and consider what these results imply for future policy.

Predictions of COVID-19 dynamics in the UK: Short-term forecasting and analysis of potential exit strategies.

Efforts to suppress transmission of SARS-CoV-2 in the UK have seen non-pharmaceutical interventions being invoked. The most severe measures to date include all restaurants, pubs and cafes being ordered to close on 20th March, followed by a "stay at home" order on the 23rd March and the closure of all non-essential retail outlets for an indefinite period. Government agencies are presently analysing how best to develop an exit strategy from these measures and to determine how the epidemic may progress once measures are lifted.

Detection of neutralising antibodies to SARS-CoV-2 to determine population exposure in Scottish blood donors between March and May 2020.

BackgroundThe progression and geographical distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United Kingdom (UK) and elsewhere is unknown because typically only symptomatic individuals are diagnosed. We performed a serological study of blood donors in Scotland in the spring of 2020 to detect neutralising antibodies to SARS-CoV-2 as a marker of past infection and epidemic progression.AimOur objective was to determine if sera from blood bank donors can be used to track the emergence and progression of the SARS-CoV-2 epidemic.

Adaptive immunity selects against malaria infection blocking mutations.

The mutation responsible for Duffy negativity, which impedes Plasmodium vivax infection, has reached high frequencies in certain human populations. Conversely, mutations capable of blocking the more lethal P. falciparum have not succeeded in malarious zones.

Detecting HLA-infectious disease associations for multi-strain pathogens.

Human Leukocyte Antigen (HLA) molecules play a vital role helping our immune system to detect the presence of pathogens. Previous work to try and ascertain which HLA alleles offer advantages against particular pathogens has generated inconsistent results. We have constructed an epidemiological model to understand why this may occur.

Diversity of HLA Class I and Class II blocks and conserved extended haplotypes in Lacandon Mayans.

Here we studied HLA blocks and haplotypes in a group of 218 Lacandon Maya Native American using a high-resolution next generation sequencing (NGS) method. We assessed the genetic diversity of HLA class I and class II in this population, and determined the most probable ancestry of Lacandon Maya HLA class I and class II haplotypes. Importantly, this Native American group showed a high degree of both HLA homozygosity and linkage disequilibrium across the HLA region and also lower class II HLA allelic diversity than most previously reported populations (including other Native American groups).

Estimating the burden of α-thalassaemia in Thailand using a comprehensive prevalence database for Southeast Asia.

Unlabelled: Severe forms of α-thalassaemia, haemoglobin H disease and haemoglobin Bart's hydrops fetalis, are an important public health concern in Southeast Asia. Yet information on the prevalence, genetic diversity and health burden of α-thalassaemia in the region remains limited. We compiled a geodatabase of α-thalassaemia prevalence and genetic diversity surveys and, using geostatistical modelling methods, generated the first continuous maps of α-thalassaemia mutations in Thailand and sub-national estimates of the number of newborns with severe forms in 2020.

Reverse immunodynamics: a new method for identifying targets of protective immunity.

Despite a dramatic increase in our ability to catalogue variation among pathogen genomes, we have made far fewer advances in using this information to identify targets of protective immunity. Epidemiological models predict that strong immune selection can cause antigenic variants to structure into genetically discordant sets of antigenic types (e.g.

The spatial epidemiology of sickle-cell anaemia in India.

Sickle-cell anaemia (SCA) is a neglected chronic disorder of increasing global health importance, with India estimated to have the second highest burden of the disease. In the country, SCA is particularly prevalent in scheduled populations, which comprise the most socioeconomically disadvantaged communities. We compiled a geodatabase of a substantial number of SCA surveys carried out in India over the last decade.

Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses.

Selective autophagy is a catabolic process with which cellular material is specifically targeted for degradation by lysosomes. The function of selective autophagic degradation of self-components in the regulation of innate immunity is still unclear. Here we show that Drosophila Kenny, the homolog of mammalian IKKγ, is a selective autophagy receptor that mediates the degradation of the IκB kinase complex.

Local substrates of non-receptor tyrosine kinases at synaptic sites in neurons.

Several non-receptor tyrosine kinase (nRTK) members are expressed in neurons of mammalian brains. Among these neuron-enriched nRTKs, two Src family kinase members (Src and Fyn) are particularly abundant at synaptic sites and have been most extensively studied for their roles in the regulation of synaptic activity and plasticity. Increasing evidence shows that the synaptic subpool of nRTKs interacts with a number of local substrates, including glutamate receptors (both ionotropic and metabotropic glutamate receptors), postsynaptic scaffold proteins, presynaptic proteins, and synapse-enriched enzymes.

Detecting signatures of past pathogen selection on human HLA loci: are there needles in the haystack?

Human leucocyte antigens (HLAs) are responsible for the display of peptide fragments for recognition by T-cell receptors. The gene family encoding them is thus integral to human adaptive immunity, and likely to be under strong pathogen selection. Despite this, it has proved difficult to demonstrate specific examples of pathogen-HLA coevolution.

Rapid mortality transition of Pacific Islands in the 19th century.

The depopulation of Pacific islands during the 16th to 19th centuries is a striking example of historical mass mortality due to infectious disease. Pacific Island populations have not been subject to such cataclysmic infectious disease mortality since. Here we explore the processes which could have given rise to this shift in infectious disease mortality patterns.

Reproduction, infection and killer-cell immunoglobulin-like receptor haplotype evolution.

Killer-cell immunoglobulin-like receptors (KIRs) are encoded by one of the most polymorphic families in the human genome. KIRs are expressed on natural killer (NK) cells, which have dual roles: (1) in fighting infection and (2) in reproduction, regulating hemochorial placentation. Uniquely among primates, human KIR genes are arranged into two haplotypic combinations: KIR A and KIR B.

Sickle haemoglobin, haemoglobin C and malaria mortality feedbacks.

Background: Sickle haemoglobin (HbS) and haemoglobin C (HbC) are both caused by point mutations in the beta globin gene, and both offer substantial malaria protection. Despite the fact that the blood disorder caused by homozygosity for HbC is much less severe than that caused by homozygosity for HbS (sickle cell anaemia), it is the sickle mutation which has come to dominate many old-world malarious regions, whilst HbC is highly restricted in its geographical distribution. It has been suggested that this discrepancy may be due to sickle cell heterozygotes enjoying a higher level of malaria protection than heterozygotes for HbC.

Understanding the contrasting spatial haplotype patterns of malaria-protective β-globin polymorphisms.

The malaria-protective β-globin polymorphisms, sickle-cell (β(S)) and β(0)-thalassaemia, are canonical examples of human adaptation to infectious disease. Occurring on distinct genetic backgrounds, they vary markedly in their patterns of linked genetic variation at the population level, suggesting different evolutionary histories. β(S) is associated with five classical restriction fragment length polymorphism haplotypes that exhibit remarkable specificity in their geographical distributions; by contrast, β(0)-thalassaemia mutations are found on haplotypes whose distributions overlap considerably.

Vaccination Drives Changes in Metabolic and Virulence Profiles of Streptococcus pneumoniae.

The bacterial pathogen, Streptococcus pneumoniae (the pneumococcus), is a leading cause of life-threatening illness and death worldwide. Available conjugate vaccines target only a small subset (up to 13) of >90 known capsular serotypes of S. pneumoniae and, since their introduction, increases in non-vaccine serotypes have been recorded in several countries: a phenomenon termed Vaccine Induced Serotype Replacement (VISR).

Epistasis and the sensitivity of phenotypic screens for beta thalassaemia.

Genetic disorders of haemoglobin, particularly the sickle cell diseases and the alpha and beta thalassaemias, are the commonest inherited disorders worldwide. The majority of affected births occur in low-income and lower-middle income countries. Screening programmes are a vital tool to counter these haemoglobinopathies by: (i) identifying individual carriers and allowing them to make informed reproductive choices, and (ii) generating population level gene-frequency estimates, to help ensure the optimal allocation of public health resources.

Pathogen selection drives nonoverlapping associations between HLA loci.

Pathogen-mediated selection is commonly invoked as an explanation for the exceptional polymorphism of the HLA gene cluster, but its role in generating and maintaining linkage disequilibrium between HLA loci is unclear. Here we show that pathogen-mediated selection can promote nonrandom associations between HLA loci. These associations may be distinguished from linkage disequilibrium generated by other population genetic processes by virtue of being nonoverlapping as well as nonrandom.

The emergence and maintenance of sickle cell hotspots in the Mediterranean.

Genetic disorders of haemoglobin (haemoglobinopathies), including the thalassaemias and sickle cell anaemia, abound in historically malarious regions, due to the protection they provide against death from severe malaria. Despite the overall spatial correlation between malaria and these disorders, inter-population differences exist in the precise combinations of haemoglobinopathies observed. Greece and Italy present a particularly interesting case study: their high frequencies of beta thalassaemia speak to a history of intense malaria selection, yet they possess very little of the strongly malaria protective mutation responsible for sickle cell anaemia, despite historical migrational links with Africa where high frequencies of sickle cell occur.