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Kemp, B.

Publications and source records attributed to Kemp, B..

4 recordsLinked to original sources

Enforced MYC expression selectively redirects transcriptional programs during human plasma cell differentiation

MYC provides a rheostat linking cell growth and division during plasma cell (PC) differentiation. Precise control of MYC is central to the network controlling differentiation. Deregulation of MYC drives transformation in aggressive B-cell neoplasms and is often accompanied by apoptotic protection conferred by BCL2. We assess how MYC and BCL2 deregulation impacts on the ability of human B-cells to complete PC differentiation. Under permissive conditions for PC differentiation we find such deregulation does not transform cells. While driving loss of normal PC surface phenotype, MYC deregulation has little impact on components of regulatory circuitry controlling B-cell identity. This contrasts with profound impact on initiation of secretory output and secretory reprogramming, coupled to dampening of XBP1 and immunoglobulin gene enhancement and a shift toward distinct metabolic programs. The establishment of this aberrant state depends on MYC homology boxes (MB0 and MBII). Dependence on MBII is profound and resolves to residue W135.

cell biology↗

Effects of pen enrichment on leg health of fast and slower-growing broiler chickens

Pen enrichment for broiler (meat-type) chickens is one of the potential strategies to stimulate locomotion and consequently contribute to leg health and welfare. This study was designed to evaluate effects of using a plethora of pen enrichments (barrier perches, angular ramps, horizontal platforms, large distance between feed and water and providing live Black Soldier fly larvae in a dustbathing area) on tibia characteristics, locomotion, leg health and home pen behaviour of fast and slower-growing broiler chickens. The experiment was set up as a 2 x 2 factorial arrangement with a total of 840 male broiler chickens in a complete randomized design (7 replicates per treatment and 30 chickens per replicate) with the following treatments: 1) pen enrichment (enriched pen or non-enriched pen); 2) broiler strain (fast-growing Ross 308 or slower-growing Hubbard JA 757). Home pen behaviour and use of enrichment were observed. At approximately 1400 and 2200 gram body weight, two chickens per pen were randomly selected and slaughtered, to investigate tibia morphological, biophysical and mechanical characteristics and leg health. Pen enrichment positively affected tibia biophysical characteristics, e.g., osseous volume ({Delta}=1.8 cm3, P=0.003), total volume ({Delta}=1.4 cm3, P=0.03) and volume fraction ({Delta}=0.02 %, P=0.002), in both fast and slower-growing chickens, suggesting that pen enrichment particularly affects ossification and mineralization mechanisms. Accordingly, locomotion and active behaviours were positively influenced by pen enrichment. However, pen enrichment resulted in lower body weight gain in both strains, which might be due to higher activity or lower feed intake as a result of difficulties of crossing the barrier perches. Regarding the strain, slower-growing chickens showed consistently more advanced tibia characteristics and more active behaviour than fast-growing chickens. It can be concluded that pen enrichment may lead to more activity and better bone development in both fast and slower-growing chickens.

animal behavior and cognition↗

Early-life feeding accelerates gut microbiome maturation in piglets

Early-life microbiome perturbations have been suggested to have important effects on host development, physiology, and behaviour, which can persist throughout life. We hypothesise that early feeding (access to a pre-weaning fibrous diet) can affect gut microbiome colonisation and development in neonatal piglets. In this longitudinal study, a customised fibrous diet was provided to early-fed piglets (EF; 6 litters) starting two days after birth until weaning (28 days of age) in addition to mothers milk, whereas control piglets (CON; 4 litters) suckled sows milk only. Rectal swabs were collected at multiple timepoints until six weeks of age (i.e., 2 weeks post-weaning) to investigate intestinal microbiota composition development over time using 16S rRNA gene profiling (n = 10 piglets per treatment). We observed a dynamic intestinal microbiota colonisation pattern during the pre-weaning period in both treatment groups, which rapidly stabilised within 2 weeks post-weaning. The microbial (alpha) diversity increased with age and seemed to reach a plateau in the early post-weaning time-point (day+5). The homogenous post-weaning microbiota was represented by microbial groups including Prevotella, Roseburia, Faecalibacterium, Ruminococcus, Megasphaera, Catenibacterium and Subdoligranulum. Remarkably, early feeding of neonatal piglets resulted in accelerated maturation of the intestinal microbiota at pre-weaning time-points, characterised by increased rate of microbial diversity and expanded colonisation of typical post-weaning associated microbial groups (mentioned above) at pre-weaning stages. The acceleration in EF piglets was illustrated by the simultaneous emergence of typical post-weaning-associated microbial groups and a more rapid decline of typical early-life/pre-weaning microbial genera. In addition, the individual eating behaviour scores of the piglets quantitatively correlated with the accelerated change of their microbiome. Overall, these findings show the importance of early-life nutritional strategies to influence the gut microbiota maturation in piglets.

microbiology↗

Ancient individuals from the North American Northwest Coast reveal 10,000 years of regional genetic continuity

Recent genome-wide studies of both ancient and modern indigenous people of the Americas have shed light on the demographic processes involved during the first peopling. The Pacific northwest coast proves an intriguing focus for these studies due to its association with coastal migration models and genetic ancestral patterns that are difficult to reconcile with modern DNA alone. Here we report the genome-wide sequence of an ancient individual known as \"Shuka Kaa\" (\"Man Ahead of Us\") recovered from the On Your Knees Cave (OYKC) in southeastern Alaska (archaeological site 49-PET-408). The human remains date to approximately 10,300 cal years before present (BP). We also analyze low coverage genomes of three more recent individuals from the nearby coast of British Columbia dating from approximately 6075 to 1750 cal years BP. From the resulting time series of genetic data, we show that the Pacific Northwest Coast exhibits genetic continuity for at least the past 10,300 cal BP. We also infer that population structure existed in the late Pleistocene of North America with Shuka Kaa on a different ancestral line compared to other North American individuals (i.e., Anzick-1 and Kennewick Man) from the late Pleistocene or early Holocene. Despite regional shifts in mitochondrial DNA haplogroups we conclude from individuals sampled through time that people of the northern Northwest Coast belong to an early genetic lineage that may stem from a late Pleistocene coastal migration into the Americas.\n\nSignificance StatementThe peopling of the Americas has been examined on the continental level with the aid of single-nucleotide polymorphism arrays, next generation sequencing, and advancements in ancient DNA, all of which have helped elucidate major population movements. Regional paleogenomic studies, however, have received less attention and may reveal a more nuanced demographic history. Here we present genomewide sequences of individuals from the northern Northwest Coast covering a time span of ~10,000 years and show that continental patterns of demography do not necessarily apply on the regional level. In comparison with existing paleogenomic data, we demonstrate that geographically linked population samples from the Northwest Coast exhibit an early ancestral lineage and find that population structure existed among Native North American groups as early as the late Pleistocene.

genomics↗