Characterization of a late transitional B cell population highly sensitive to BAFF-mediated homeostatic proliferation

We have characterized a distinct, late transitional B cell subset, CD21int transitional 2 (T2) B cells. In contrast to early transitional B cells, CD21int T2 B cells exhibit augmented responses to a range of potential microenvironmental stimuli. Adoptive transfer studies demonstrate that this subset is an immediate precursor of both follicular mature and marginal zone (MZ) B cells. In vivo, a large percentage of CD21int T2 B cells has entered the cell cycle, and the cycling subpopulation exhibits further augmentation in mitogenic responses and B cell-activating factor of the TNF family (BAFF) receptor expression. Consistent with these features, CD21int T2 cells exhibit preferential responses to BAFF-facilitated homeostatic signals in vivo. In addition, we demonstrate that M167 B cell receptor (BCR) idiotypic-specific B cells are first selected within the cycling CD21int T2 population, ultimately leading to preferential enrichment of these cells within the MZ B cell compartment. These data, in association with the coordinate role for BAFF and microenvironmental cues in determining the mature BCR repertoire, imply that this subset functions as a unique selection point in peripheral B cell development

Final Report: Evaluation of the AIME Outreach Program

The AIME (Australian Indigenous Mentoring Experience) Program was established in 2005 when 25 students from the University of Sydney volunteered to work with 25 Indigenous children from local high schools. Since 2005 more than 3000 mentors have been recruited to work with 3542 Indigenous school students in New South Wales, Queensland and Victoria. The AIME Program is based on the recruitment of university students as mentors who provide advice and personal support to Indigenous school mentees from years 7 to 12. Its overall goals are to improve retention rates of Indigenous high school students to Year 12 and to encourage the transition of Indigenous students to university

Infinite families of superintegrable systems separable in subgroup coordinates

A method is presented that makes it possible to embed a subgroup separable superintegrable system into an infinite family of systems that are integrable and exactly-solvable. It is shown that in two dimensional Euclidean or pseudo-Euclidean spaces the method also preserves superintegrability. Two infinite families of classical and quantum superintegrable systems are obtained in two-dimensional pseudo-Euclidean space whose classical trajectories and quantum eigenfunctions are investigated. In particular, the wave-functions are expressed in terms of Laguerre and generalized Bessel polynomials.Comment: 19 pages, 6 figure

In search of animal normativity : a framework for studying social norms in non-human animals

Funding: K. A. and E. W. were supported by the Templeton World Charity Foundation through the Diverse Intelligence initiative. K. A. was supported by SSHRC 435-2022-0749. S. F. B. was supported by NSF 2127375, NSF SES 1919305, and TWCF0471. T. G. was supported by Swiss National Science Foundation PCEFP1_186832. C. H. was supported by European Union's 8th Framework Programme, Horizon 2020 802719. L. M. H. was supported by NIH U42 OD013117-15A. C. K. was supported by TWCF-20647 and the CIFAR Azrieli Global Scholars program. L. V. L. was supported by the Max Planck Society. J. T. was supported by NIH R21 MH129902 and NIH R01 AG071173.Social norms – rules governing which behaviours are deemed appropriate or inappropriate within a given community – are typically taken to be uniquely human. Recently, this position has been challenged by a number of philosophers, cognitive scientists, and ethologists, who have suggested that social norms may also be found in certain non-human animal communities. Such claims have elicited considerable scepticism from norm cognition researchers, who doubt that any non-human animals possess the psychological capacities necessary for normative cognition. However, there is little agreement among these researchers about what these psychological prerequisites are. This makes empirical study of animal social norms difficult, since it is not clear what we are looking for and thus what should count as behavioural evidence for the presence (or absence) of social norms in animals. To break this impasse, we offer an approach that moves beyond contested psychological criteria for social norms. This approach is inspired by the animal culture research program, which has made a similar shift away from heavily psychological definitions of ‘culture’ to become organised around a cluster of more empirically tractable concepts of culture. Here, we propose an analogous set of constructs built around the core notion of a normative regularity, which we define as a socially maintained pattern of behavioural conformity within a community. We suggest methods for studying potential normative regularities in wild and captive primates. We also discuss the broader scientific and philosophical implications of this research program with respect to questions of human uniqueness, animal welfare and conservation.Publisher PDFPeer reviewe

An infinite family of superintegrable Hamiltonians with reflection in the plane

We introduce a new infinite class of superintegrable quantum systems in the plane. Their Hamiltonians involve reflection operators. The associated Schr\"odinger equations admit separation of variables in polar coordinates and are exactly solvable. The angular part of the wave function is expressed in terms of little -1 Jacobi polynomials. The spectra exhibit "accidental" degeneracies. The superintegrability of the model is proved using the recurrence relation approach. The (higher-order) constants of motion are constructed and the structure equations of the symmetry algebra obtained.Comment: 19 page

An Early Beaker funerary monument at Porton Down, Wiltshire

Excavation of an Early Beaker-Early Bronze Age funerary monument at Porton Down revealed an unusually complex burial sequence of 12 individuals, spanning four centuries, including eight neonates or infants and only one probable male, surrounded by a segmented ring-ditch. In the centre was a large grave which contained the disturbed remains of an adult female, accompanied by a Beaker, which had probably been placed within a timber chamber and later ‘revisited’ on one or more occasions. This primary burial and an antler pick from the base of the ring-ditch provided identical Early Beaker radiocarbon dates. Two burials were accompanied by a Food Vessel and a miniature Collared Urn respectively, others were unaccompanied, and there was a single and a double cremation burial, both within inverted Collared Urns. A C-shaped enclosure nearby may have been contemporary with the funerary monument, but its date and function are uncertain. Other features included an Early Neolithic pit which contained a significant assemblage of worked flint, and several Middle Bronze Age ditches and a Late Bronze Age ‘Wessex Linear’ ditch that reflect later prehistoric land divisions probably related to stock control

Whole-Genome Sequencing-Based Characterization of 100 Listeria monocytogenes Isolates Collected from Food Processing Environments over a Four-Year Period

Listeria monocytogenes is frequently found in foods and processing facilities, where it can persist, creating concerns for the food industry. Its ability to survive under a wide range of environmental conditions enhances the potential for cross-contamination of the final food products, leading to possible outbreaks of listeriosis. In this study, whole-genome sequencing (WGS) was applied as a tool to characterize and track 100 L. monocytogenes isolates collected from three food processing environments. These WGS data from environmental and food isolates were analyzed to (i) assess the genomic diversity of L. monocytogenes, (ii) identify possible source(s) of contamination, cross-contamination routes, and persistence, (iii) detect absence/presence of antimicrobial resistance-encoding genes, (iv) assess virulence genotypes, and (v) explore in vivo pathogenicity of selected L. monocytogenes isolates carrying different virulence genotypes. The predominant L. monocytogenes sublineages (SLs) identified were SL101 (21%), SL9 (17%), SL121 (12%), and SL5 (12%). Benzalkonium chloride (BC) tolerance-encoding genes were found in 62% of these isolates, a value that increased to 73% among putative persistent subgroups. The most prevalent gene was emrC followed by bcrABC, qacH-Tn6188, and qacC. The L. monocytogenes major virulence factor inlA was truncated in 31% of the isolates, and only one environmental isolate (L. monocytogenes CFS086) harbored all major virulence factors, including Listeria pathogenicity island 4 (LIPI-4), which has been shown to confer hypervirulence. A zebrafish embryo infection model showed a low (3%) embryo survival rate for all putatively hypervirulent L. monocytogenes isolates assayed. Higher embryo survival rates were observed following infection with unknown virulence potential (20%) and putatively hypovirulent (53 to 83%) L. monocytogenes isolates showing predicted pathogenic phenotypes inferred from virulence genotypes

Families of superintegrable Hamiltonians constructed from exceptional polynomials

We introduce a family of exactly-solvable two-dimensional Hamiltonians whose wave functions are given in terms of Laguerre and exceptional Jacobi polynomials. The Hamiltonians contain purely quantum terms which vanish in the classical limit leaving only a previously known family of superintegrable systems. Additional, higher-order integrals of motion are constructed from ladder operators for the considered orthogonal polynomials proving the quantum system to be superintegrable

Loss of synergistic transcriptional feedback loops drives diverse B-cell cancers

BACKGROUND: The most common B-cell cancers, chronic lymphocytic leukemia/lymphoma (CLL), follicular and diffuse large B-cell (FL, DLBCL) lymphomas, have distinct clinical courses, yet overlapping cell-of-origin . Dynamic changes to the epigenome are essential regulators of B-cell differentiation. Therefore, we reasoned that these distinct cancers may be driven by shared mechanisms of disruption in transcriptional circuitry. METHODS: We compared purified malignant B-cells from 52 patients with normal B-cell subsets (germinal center centrocytes and centroblasts, naïve and memory B-cells) from 36 donor tonsils using \u3e325 high-resolution molecular profiling assays for histone modifications, open chromatin (ChIP-, FAIRE-seq), transcriptome (RNA-seq), transcription factor (TF) binding, and genome copy number (microarrays). FINDINGS: From the resulting data, we identified gains in active chromatin in enhancers/super-enhancers that likely promote unchecked B-cell receptor signaling, including one we validated near the immunoglobulin superfamily receptors FCMR and PIGR. More striking and pervasive was the profound loss of key B-cell identity TFs, tumor suppressors and their super-enhancers, including EBF1, OCT2(POU2F2), and RUNX3. Using a novel approach to identify transcriptional feedback, we showed that these core transcriptional circuitries are self-regulating. Their selective gain and loss form a complex, iterative, and interactive process that likely curbs B-cell maturation and spurs proliferation. INTERPRETATION: Our study is the first to map the transcriptional circuitry of the most common blood cancers. We demonstrate that a critical subset of B-cell TFs and their cognate enhancers form self-regulatory transcriptional feedback loops whose disruption is a shared mechanism underlying these diverse subtypes of B-cell lymphoma. FUNDING: National Institute of Health, Siteman Cancer Center, Barnes-Jewish Hospital Foundation, Doris Duke Foundation