Immunohistochemical ALK Expression in Granular Cell Atypical Fibroxanthoma: A Diagnostic Pitfall for ALK-Rearranged Non-neural Granular Cell Tumor.

ABSTRACT: Atypical fibroxanthoma (AFX) is a neoplasm that most commonly occurs on sun-damaged skin of the head and neck in elderly patients and that usually exhibits indolent clinical behavior with complete excision. The granular cell variant of AFX demonstrates overlapping histopathologic features with dermal non-neural granular cell tumor (NNGCT), which typically arises on the extremities of young to middle aged adults with rare reports of regional metastasis. A subset of NNGCT harbors ALK rearrangements and expresses ALK by immunohistochemistry. Here, we present 2 cases of granular cell AFX occurring on the scalp of males aged 73 and 87 with ALK expression by immunohistochemistry and no evidence of an ALK rearrangement on fluorescence in situ hybridization, representing a diagnostic pitfall for NNGCT.

Phased Patagonian Ice Sheet response to Southern Hemisphere atmospheric and oceanic warming between 18 and 17 ka.

The onset of deglaciation in the Southern Hemisphere mid-latitudes has been attributed to the southward transmission of climate anomalies in response to slow-down of Atlantic meridional overturning circulation (AMOC) during Heinrich Stadial 1 (HS-1; 18-14.6 ka). However, inferences on the response of former ice sheets to sub-millennial palaeoclimate shifts are limited by a shortage of high-resolution terrestrial archives. Here we use a ~1000-year duration, annually-resolved lake sediment record to investigate the deglacial retreat dynamics of the Lago General Carrera-Buenos Aires ice lobe (46.5°S) of the former Patagonian Ice Sheet. We attribute the onset of glacier retreat at 18.0 ± 0.14 cal ka BP to abrupt southward migration of the Southern Westerly Winds that enhanced solar radiation receipt (and ablation) at the ice sheet surface. We infer that accelerated retreat from 17.77 ± 0.13 cal ka BP represents a lagged Southern Hemisphere response to gradual ocean-atmosphere warming associated with the centennial-scale transmission of Northern Hemisphere climate anomalies through the oceanic bipolar seesaw. By 17.38 ± 0.12 cal ka BP, the glacier margin had receded into a deepening proglacial lake, instigating sustained calving losses and more rapid ice recession.

The resilience of postglacial hunter-gatherers to abrupt climate change.

Understanding the resilience of early societies to climate change is an essential part of exploring the environmental sensitivity of human populations. There is significant interest in the role of abrupt climate events as a driver of early Holocene human activity, but there are very few well-dated records directly compared with local climate archives. Here, we present evidence from the internationally important Mesolithic site of Star Carr showing occupation during the early Holocene, which is directly compared with a high-resolution palaeoclimate record from neighbouring lake beds. We show that-once established-there was intensive human activity at the site for several hundred years when the community was subject to multiple, severe, abrupt climate events that impacted air temperatures, the landscape and the ecosystem of the region. However, these results show that occupation and activity at the site persisted regardless of the environmental stresses experienced by this society. The Star Carr population displayed a high level of resilience to climate change, suggesting that postglacial populations were not necessarily held hostage to the flickering switch of climate change. Instead, we show that local, intrinsic changes in the wetland environment were more significant in determining human activity than the large-scale abrupt early Holocene climate events.

Visualizing tephra deposits and sedimentary processes in the marine environment: The potential of X-ray microtomography.

Localized tephra deposition in marine sequences is the product of many complex primary and secondary depositional processes. These can significantly influence the potential applicability of tephra deposits as isochronous marker horizons and current techniques, used in isolation, may be insufficient to fully unravel these processes. Here we demonstrate the innovative application of X-ray microtomography (µCT) to successfully identify tephra deposits preserved within marine sediments and use these parameters to reconstruct their internal three-dimensional structure. Three-dimensional visualizations and animations of tephra dispersal in the sediment permit a more thorough assessment of postdepositional processes revealing a number of complex microsedimentological features that are not revealed by conventional methods. These features include bioturbation burrows and horizontally discontinuous tephra packages, which have important ramifications for the stratigraphic placement of the isochron in a sedimentary sequence. Our results demonstrate the potential for utilizing rigorous two and three-dimensional microsedimentological analysis of the ichnofabric to enhance and support the use of tephra deposits as isochronous marker horizons and to identify the stratigraphic position that best reflects the primary fallout of ash. The application also provides an exceptional insight into the style and rate of sedimentation processes and permits an assessment of the stratigraphic integrity of a tephra deposit. We discuss the possibility of applying these µCT methods to the identification of cryptotephras within various paleoclimatic sequences and to enhance our understanding of marine sedimentation processes.

Brilliant violet fluorophores: a new class of ultrabright fluorescent compounds for immunofluorescence experiments.

The Nobel Prize in Chemistry was awarded in 2000 for the discovery of conductive organic polymers, which have subsequently been adapted for applications in ultrasensitive biological detection. Here, we report the first use of this new class of fluorescent probes in a diverse range of cytometric and imaging applications. We demonstrate that these "Brilliant Violet" reporters are dramatically brighter than other UV-violet excitable dyes, and are of similar utility to phycoerythrin (PE) and allophycocyanin (APC). They are thus ideally suited for cytometric assays requiring high sensitivity, such as MHC-multimer staining or detection of intracellular antigens. Furthermore, these reporters are sensitive and spectrally distinct options for fluorescence imaging, two-photon microscopy and imaging cytometry. These ultra-bright materials provide the first new high-sensitivity fluorescence probes in over 25 years and will have a dramatic impact on the design and implementation of multicolor panels for high-sensitivity immunofluorescence assays.