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Glycolytic enzymes are challenging drug targets due to their highly conserved active sites and phosphorylated substrates. Here, the authors identify fast acting allosteric inhibitors of Trypanosoma brucei phosphofructokinase that block trypanosome glycolysis and provide cure evidence in murine model.

Sulfur isotope excursions in skeletal collagen samples from Eurasia suggest rapidly changing biogeochemical processes across the region from about 30,000 to 15,000 years ago, potentially related to changing permafrost conditions.

Tracking temporal patterns of proboscidean dental evolution in relation to diet and environment, the authors find that the effects of diet and environment are decoupled, and evolution of dentition alternated between directional change at times of high selective pressure and stasis when selective regimes reversed.

Body size reduction in mammals is accompanied by only a moderate reduction in brain size, so that the brains of dwarfs are proportionately larger than those of giants. Here, the brains of extinct dwarf hippos from the island of Madagascar are shown to be disproportionately very much smaller than those of their closest mainland relatives. If this trend no longer holds true on islands, it may explain the exceptionally small brain size of the diminutive hominin, Homo floresiensis.

To test whether a behavioural change can lead to morphological evolution, stable isotopes in tooth enamel are used to show that archaic elephants were feeding on grassland millions of years before their teeth adapted by becoming high-crowned.

Giant deer on the Isle of Man around 9,000 years ago may have been the last of the line.

Radiocarbon dates, stable isotope data and DNA sequencing indicate an Elasmotheriinae/Rhinocerotinae split by the Eocene period, and the extinction of Elasmotherium sibiricum no later than 39,000 years ago, to which its specialized diet was probably a contributing factor.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Siberian mammoth genomes from the Early and Middle Pleistocene subepochs reveal adaptive changes and a key hybridization event, highlighting the value of deep-time palaeogenomics for studies of speciation and long-term evolutionary trends.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Epidemiological analyses coupled with immunological phenotyping suggest that humoral immunity induced by COVID-19 vaccines wanes more rapidly in individuals with severe obesity compared to individuals with a BMI within the normal range.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Follicular helper T (T_FH) cells provide survival and selection signals to germinal center B cells. Here, Carola Vinuesa and colleagues describe a regulatory T cell subset that co-opts the differentiation program of T_FH cells and limits their numbers in vivo. Ablation of these T_FH-like, T regulatory cells alters the number of antigen-specific B cells suggesting regulatory T cells modulate germinal center responses.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

An extensive profile of DNA methylation in neuronal and non-neuronal cells across four brain regions is reported, showing that differential epigenetic marks are enriched for DNA variants associated with neuropsychiatric traits.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Were the Late Pleistocene extinctions of large mammals the result of climate change or big-game hunting by humans? Reconstructing the biology of extinct species provides clues to the answer.

When, where and why was the two-humped Bactrian camel first domesticated? A new analysis tackles these issues, drawing on a variety of archaeological evidence (and including discussion of a translation of a twelfth-century Chinese manual on camel husbandry). The answer to the first question remains pretty much a mystery. As to the second and third, the authors surmise that the likeliest answers are Kazakhstan, northern Mongolia or northern China, and for meat.

In vivo, in vitro and in silico experiments demonstrate that interface residues of homomeric proteins are enriched toward protein C termini to avoid premature assembly and aggregation.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Here, Ratmann et al. show how viral deep sequencing data can be used to reconstruct HIV-1 transmission networks and to infer the direction of transmission in these networks.

Wiskott-Aldrich syndrome protein (WASp) is essential for controlling the cytoskeleton, but its function in innate immunity is unclear. Here the authors show that WASp deficiency is associated with dysregulated septin cage formation, excessive inflammasome activation, elevated immune cell death and reduced bacterial clearance.

An expanded repetition of a DNA sequence within the C9orf72 gene is the most common genetic cause for motor neuron disease and frontotemporal dementia. In this study, the authors show that this expansion causes increased genomic breaks and reduces the cell's ability to repair the breaks, ultimately leading to neuronal cell death.

Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

Richard Houlston and colleagues report a genome-wide association study for colorectal cancer. They report three loci newly associated with colorectal cancer, bringing the total number of common susceptibility loci to 20.

Recent findings have demonstrated that Polycomb repressive complexes (PRCs) control gene expression through their co-recruitment to specific CpG island elements with transcription factors and non-coding RNAs. Moreover, they revealed that the interplay between PRC1 and PRC2 to achieve transcriptional repression is more intricate than was previously thought.