Light-Controllable Binary Switch Activation of CAR T Cells.

Major challenges to chimeric antigen receptor (CAR) T cell therapies include uncontrolled immune activity, off-tumor toxicities and tumor heterogeneity. To overcome these challenges, we engineered CARs directed against small molecules. By conjugating the same small molecule to distinct tumor-targeting antibodies, we show that small molecule specific-CAR T cells can be redirected to different tumor antigens.

A meta-analytical evaluation of the effects of high-salt water intake on beef cattle.

Adequate drinking water is essential to maintain acceptable production levels in beef cattle operations. In the context of global climate change, the water scarcity forecasted for the future is a growing concern and it would determine an increase in the use of poorer quality water by the agricultural sector in many parts of the world. However, consumption of high-salt water by cattle has consequences often overlooked.

Use of Unpalatable Forages by Ruminants: The Influence of Experience with the Biophysical and Social Environment.

Unpalatable forage resources (low nutrient density, potentially toxic metabolites) are widespread and represent a challenge for ruminant nutrition, health, and welfare. Our objective was to synthesize the role of biophysical and social experience on the use of unpalatable forages by ruminants, and highlight derived behavioural solutions for the well-being of soils, plants, and animals. Environmental experiences early in life modulate gene expression and promote learning, which alters morpho-physiological and psychological mechanisms that modify behavioural responses and change food and habitat selection.

RATA: A method for high-throughput identification of RNA bound transcription factors.

Long non-coding RNAs (lncRNAs) regulate critical cellular processes and their dysregulation contributes to multiple diseases. Although only a few lncRNAs have defined mechanisms, many of these characterized lncRNAs interact with transcription factors to regulate gene expression, suggesting a common mechanism of action. Identifying RNA-bound transcription factors is especially challenging due to inefficient RNA immunoprecipitation and low abundance of many transcription factors.

Recurrent ubiquitin B silencing in gynecological cancers establishes dependence on ubiquitin C.

Transcriptional repression of ubiquitin B (UBB) is a cancer-subtype-specific alteration that occurs in a substantial population of patients with cancers of the female reproductive tract. UBB is 1 of 2 genes encoding for ubiquitin as a polyprotein consisting of multiple copies of ubiquitin monomers. Silencing of UBB reduces cellular UBB levels and results in an exquisite dependence on ubiquitin C (UBC), the second polyubiquitin gene.

High-sulfate water consumption determines intake and metabolic responses to protein supplementation in lambs consuming low-quality forage.

Twenty Hampshire lambs (31 ± 4 kg BW) in individual metabolism cages were used in a 10-treatment by 2-period ( = 4) trial to evaluate the interaction between protein supplementation and sulfate water on intake and metabolic responses when lambs were fed low-quality grass hay (; 6.4% CP, 79.5% NDF).

The physiological consequences of ingesting a toxic plant (Diplotaxis tenuifolia) influence subsequent foraging decisions by sheep (Ovis aries).

Toxins and nutrients interact and define herbivores' experiences with toxic plants. However, there are still open questions about the mechanisms by which nutrient-toxin interactions affect experience and as a consequence foraging decisions by consumers. This study provides a deeper insight into such mechanisms by using supplemental nutrients, a toxic plant typically avoided by herbivores (wild rocket; Diplotaxis tenuifolia), and a small ruminant (sheep; Ovis aries) as models.

The lncRNA SLNCR1 Mediates Melanoma Invasion through a Conserved SRA1-like Region.

Long non-coding RNAs (lncRNAs) have been implicated in numerous physiological processes and diseases, most notably cancers. However, little is known about the mechanism of many functional lncRNAs. We identified an abundantly expressed lncRNA associated with decreased melanoma patient survival.

How the foraging decisions of a small ruminant are influenced by past feeding experiences with low-quality food.

Feeding experiences with low-quality foods can be improved when these foods are ingested in close temporal association with foods of higher nutritional quality. However, preference for low-quality foods in nature seems to be rather insensitive to past positive experiences and more related to their intrinsic nutritional value. An explanation for this observation is still lacking, mainly because little is known about how herbivores use information about low-quality foods during foraging.

Free availability of high-energy foods led to energy over-ingestion and protein under-ingestion in choice-fed broilers.

The objective of this study was to compare energy and protein content of the diet selected by choice-fed broilers with that of broilers fed a balanced diet. One hundred and eighty 1-day-old male broilers were randomly assigned in groups of 10 to one of three experimental treatments (n = 6). Control broilers were fed a standard balanced diet, whereas choice-fed broilers were fed three foods which were more concentrated (Choice C+ treatment) or less concentrated (Choice C- treatment) in protein, carbohydrate or fat.

Expression of conditioned preference for low-quality food in sheep is modulated by foraging costs.

Past positive experiences can increase herbivores' motivation to eat low-quality foods. However, this is not always translated into a higher preference for low-quality foods in choice tests among foods of higher nutritional quality. Foraging behavior is also affected by properties of the feeding context because the quality and abundance of foods in nature change in time and space.

Effects of supplementing endophyte-infected tall fescue with sainfoin and polyethylene glycol on the physiology and ingestive behavior of sheep.

Tannins in sainfoin (Onobrychis viciifolia) may bind to alkaloids in endophyte-infected tall fescue [E+; Lolium arundinaceum (Schreb.) Darbysh.] and attenuate toxicosis.

Effect of protein supplementation on tropical grass hay utilization by beef steers drinking saline water.

An experiment was conducted to assess the impact of increasing levels of supplemental soybean meal (SBM; 45.7% CP) in cattle consuming tropical grass hay (Panicum maximum cultivar Gatton; 7.0% CP and 81.

Induction of low-nutritious food intake by subsequent nutrient supplementation in sheep (Ovis aries).

Acceptance of and preference for a particular food depends not only on its intrinsic (e.g. nutritional) properties but also on expected or recent food experiences.

Alternative methods for characterization of extracellular vesicles.

Extracellular vesicles (ECVs) are nano-sized vesicles released by all cells in vitro as well as in vivo. Their role has been implicated mainly in cell-cell communication, but also in disease biomarkers and more recently in gene delivery. They represent a snapshot of the cell status at the moment of release and carry bioreactive macromolecules such as nucleic acids, proteins, and lipids.

Devaluation of low-quality food during early experience by sheep.

A ruminant's early experience with low-quality food (LQF) is expected to increase its acceptance and preference in adulthood. Contrarily, we found that experienced sheep (ES) exposed to mature oat hay early in life ate less of this LQF than inexperienced sheep (IS). A possibility is that ES might have devaluated the LQF through continuous comparisons against high-quality food (HQF) supplements (sunflower meal and ground corn) that were simultaneously available during early experience.

Early experience with diverse foods increases intake of nonfamiliar flavors and feeds in sheep.

This study determined whether early experiences by sheep with monotonous or diverse diets influence intake of unfamiliar flavors and feeds later in life. Thirty 2-mo-old lambs were randomly assigned to 3 treatment diets (n = 10): diverse (DIV), diverse with plant toxins (DIV+T), and monotonous (MON). Lambs in DIV received in 9 successive periods of exposure 4-way choice combinations of 2 foods high in energy and 2 foods high in protein from an array of 6 foods: 3 high in energy [beet pulp, oat grain, and a mix of milo:grape pomace (60:40)] and 3 high in digestible protein (DP) (soybean meal, alfalfa, corn gluten meal).

Relationships between early experience to dietary diversity, acceptance of novel flavors, and open field behavior in sheep.

This study determined whether early experiences by sheep to monotonous or diverse diets influence: (1) plasmatic profiles of cortisol, a hormone involved in stress responses by mammals, before and after an ACTH challenge, (2) the readiness to eat new foods in a new environment, (3) general fearfulness and response to separation--as measured by the open field test (OFT) and stress induced hyperthermia (SIH)--and (4) the link between (2) and (3). Thirty, 2-mo-old lambs were randomly assigned to 3 treatments (10 lambs/treatment). Lambs in one treatment (Diversity--DV) received in successive periods of exposure all possible 4-way choice combinations of 2 foods high in energy and 2 foods high in protein from an array of 6 foods: 3 high in energy (beet pulp, oat grain, and a mix of grape pomace:milo [40:60]) and 3 high in protein (soybean meal, alfalfa, corn gluten meal).

Mechanisms of intake induction of a low-nutritious food in sheep (Ovis aries).

Intake induction refers to the phenomenon by which animals increase consumption of a less-valued meal when followed by a highly-preferred food relative to when followed by no food or by the same less-preferred food. In the Training phase of the present experiment, we assessed the induction effect in sheep using a within-subject design where learning could be tested while controlling for digestive state. Results showed that, once intake reached stability, subjects ate more low-nutritious food (oat hay) when followed than when preceded by a preferred food (soybean meal), supporting the learning hypothesis of induction.

A new device for rapid isolation by size and characterization of rare circulating tumor cells.

Background: Circulating tumor cells (CTCs) likely derive from clones in the primary tumor, suggesting that they can be used for all biological tests applying to the primary cells.

Materials And Methods: The ScreenCell® devices are single-use and low-cost innovative devices that use a filter to isolate and sort tumor cells by size.

Results: The ScreenCell® Cyto device is able to isolate rare, fixed, tumor cells, with a high recovery rate.

TGF-beta1 interactome: metastasis and beyond.

The ubiquitous cytokine transforming growth factor-beta1 (TGF-beta1) is one of the most potent metastatic inducers. Functional interactomic mapping using high-throughput proteomic and genomic data provides valuable insights into the regulation of tumor suppressive and metastatic attributes of TGF-beta1. Polarity changes of the TGF-beta1 interactome at a given time contributes to these contrasting effects.

Role of early experience in the development of preference for low-quality food in sheep.

Domestic ruminant selectivity induces floristic changes in pasturelands, risking sustainability and limiting the subsequent availability of susceptible plant species. Development of preferences for species of lower nutritional quality may help to overcome those problems. In this study, we tested the hypothesis that early experience of sheep with a low-quality food (LQF) in a nutritional enriched context increases preference for LQF in adulthood.

Noninvasive detection of EGFR T790M in gefitinib or erlotinib resistant non-small cell lung cancer.

Purpose: Tumors from 50% of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer patients that develop resistance to gefitinib or erlotinib will contain a secondary EGFR T790M mutation. As most patients do not undergo repeated tumor biopsies we evaluated whether EGFR T790M could be detected using plasma DNA.

Experimental Design: DNA from plasma of 54 patients with known clinical response to gefitinib or erlotinib was extracted and used to detect both EGFR-activating and EGFR T790M mutations.

s-RT-MELT for rapid mutation scanning using enzymatic selection and real time DNA-melting: new potential for multiplex genetic analysis.

The rapidly growing understanding of human genetic pathways, including those that mediate cancer biology and drug response, leads to an increasing need for extensive and reliable mutation screening on a population or on a single patient basis. Here we describe s-RT-MELT, a novel technology that enables highly expanded enzymatic mutation scanning in human samples for germline or low-level somatic mutations, or for SNP discovery. GC-clamp-containing PCR products from interrogated and wild-type samples are hybridized to generate mismatches at the positions of mutations over one or multiple sequences in-parallel.