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Initial seeding of the embryonic thymus by immune-restricted lympho-myeloid progenitors

The final stages of restriction to the T cell lineage occur in the thymus after the entry of thymus-seeding progenitors (TSPs). The identity and lineage potential of TSPs remains unclear. Because the first embryonic TSPs enter a non-vascularized thymic rudiment, we were able to directly image and establish the functional and molecular properties of embryonic thymopoiesis-initiating progenitors (T-

Hotspots of uncertainty in land-use and land-cover change projections : a global-scale model comparison

Model-based global projections of future land-use and land-cover (LULC) change are frequently used in environmental assessments to study the impact of LULC change on environmental services and to provide decision support for policy. These projections are characterized by a high uncertainty in terms of quantity and allocation of projected changes, which can severely impact the results of environmen

Rare novel variants in the ZIC3 gene cause X-linked heterotaxy

Variants in the ZIC3 gene are rare, but have demonstrated their profound clinical significance in X-linked heterotaxy, affecting in particular male patients with abnormal arrangement of thoracic and visceral organs. Several reports have shown relevance of ZIC3 gene variants in both familial and sporadic cases and with a predominance of mutations detected in zinc-finger domains. No studies so far h

An enzyme activity as a potential biomarker for Alzheimer's disease.

Background: Six different N-terminal amyloid precursor protein (APP) fragments, with molecular weight ∼12 kDa, have previously been identified in human cerebrospinal fluid (CSF). In a pilot study, both the sum of their concentrations, measured by western blot, and the relative abundance pattern, measured by mass spectrometry, were different in Alzheimer's disease (AD) patients compared to healthy

CRY2 and FBXL3 Cooperatively Degrade c-MYC

For many years, a connection between circadian clocks and cancer has been postulated. Here we describe an unexpected function for the circadian repressor CRY2 as a component of an FBXL3-containing E3 ligase that recruits T58-phosphorylated c-MYC for ubiquitylation. c-MYC is a critical regulator of cell proliferation; T58 is central in a phosphodegron long recognized as a hotspot for mutation in ca

Into the Andes : multiple independent colonizations drive montane diversity in the Neotropical clearwing butterflies Godyridina

Understanding why species richness peaks along the Andes is a fundamental question in the study of Neotropical biodiversity. Several biogeographic and diversification scenarios have been proposed in the literature, but there is confusion about the processes underlying each scenario, and assessing their relative contribution is not straightforward. Here, we propose to refine these scenarios into a

Determination of 3′-phosphoadenosine-5′-phosphosulfate in cells and Golgi fractions using hydrophilic interaction liquid chromatography–mass spectrometry

3′-Phosphoadenosine-5′-phosphosulfate (PAPS) is a key player in the sulfation of biomolecules, but methods for selective measurements are lacking. A liquid chromatography–mass spectrometry (LC–MS) approach for measuring PAPS was developed. A central feature of the method was employing hydrophilic interaction liquid chromatography (HILIC), which is highly suited for separating very polar/charged co

Integrative experimental characterization and engineering modeling of single-dowel connections in LVL

In order to be able to realistically and consistently elucidate and subsequently simulate the load–displacement behavior of single-dowel connections, the material behavior of the individual components, namely steel dowels and wood, needs to be investigated. The behavior of slotted-in, single-dowel steel-to-laminated veneer lumber (LVL) connections with dowel diameters of 12 and 20 mm is thoroughly

A 3.5-6.8GHz wide-bandwidth DTC-assisted fractional-N all-digital PLL with a MASH ΔΣ TDC for low in-band phase noise

We present a digital-to-time converter (DTC)-assisted fractional-N wide-bandwidth all-digital PLL (ADPLL). It employs a MASH ΔΣ time-to-digital converter (TDC) to achieve low in-band phase noise, and a wide-tuning range digitally-controlled oscillator (DCO). Fabricated in 40nm CMOS, the ADPLL consumes 10.7 mW while outputting 1.73 to 3.38 GHz (after a ÷2 division) and achieves better than -109 dBc