Overgeneralization of autonomic defensive reactions in obesity.

Generalizing defensive responses to new stimuli resembling learned threats is an adaptive process within an ever-changing environment. However, evaluation mechanisms excessively biased toward generalization (i.e.

Medial anterior prefrontal cortex stimulation downregulates implicit reactions to threats and prevents the return of fear.

Downregulating emotional overreactions toward threats is fundamental for developing treatments for anxiety and post-traumatic disorders. The prefrontal cortex (PFC) is critical for top-down modulatory processes, and despite previous studies adopting repetitive transcranial magnetic stimulation (rTMS) over this region provided encouraging results in enhancing extinction, no studies have hitherto explored the effects of stimulating the medial anterior PFC (aPFC, encompassing the Brodmann area 10) on threat memory and generalization. Here we showed that rTMS over the aPFC applied before threat memory retrieval immediately decreases implicit reactions to learned and novel stimuli in humans.

Hippocampus-to-amygdala pathway drives the separation of remote memories of related events.

The mammalian brain can store and retrieve memories of related events as distinct memories and remember common features of those experiences. How it computes this function remains elusive. Here, we show in rats that recent memories of two closely timed auditory fear events share overlapping neuronal ensembles in the basolateral amygdala (BLA) and are functionally linked.

Stabilizing Immature Dendritic Spines in the Auditory Cortex: A Key Mechanism for mTORC1-Mediated Enhancement of Long-Term Fear Memories.

Mammalian target of rapamycin (mTOR) pathway has emerged as a key molecular mechanism underlying memory processes. Although mTOR inhibition is known to block memory processes, it remains elusive whether and how an enhancement of mTOR signaling may improve memory processes. Here we found in male mice that the administration of VO-OHpic, an inhibitor of the phosphatase and tensin homolog (PTEN) that negatively modulates AKT-mTOR pathway, enhanced auditory fear memory for days and weeks, while it left short-term memory unchanged.

Prior fear learning enables the rapid assimilation of new fear memories directly into cortical networks.

Long-term memory formation involves the reorganization of brain circuits, termed system consolidation. Whether and how a prior fear experience influences system consolidation of new memories is poorly understood. In rats, we found that prior auditory fear learning allows the secondary auditory cortex to immediately encode new auditory memories, with these new memories purely requiring the activation of cellular mechanisms of synaptic consolidation within secondary auditory cortex.

Identification of the main contributors to blood culture contamination at a tertiary care academic medical center.

Background: Blood culture contamination poses an issue to all hospital systems worldwide because of the associated costs of extended length of stays, unnecessary antibiotic therapy, and additional laboratory testing that are preventable with proper handling and collection techniques.

Methods: In our study, multiple units, staff, and collection methods were compared to determine the primary culprits of contamination from a tertiary care academic medical center, which includes a pediatric hospital and both adult and pediatric emergency departments.

Results: Over 33 months, 2,083 out of 88,322 total blood cultures collected were contaminated, with an overall contamination rate of 2.

Sleep Deprivation During Memory Consolidation, but Not Before Memory Retrieval, Widens Threat Generalization to New Stimuli.

Past aversive experiences shape our ability to deal with future dangers, through the encoding of implicit and explicit memory traces and through the ability to generalize defensive reactions to new stimuli resembling learned threats. Numerous evidence demonstrate that sleep is important for the consolidation of memories related to threatening events. However, there is a lack of studies examining the effects of sleep deprivation on the retrieval of consolidated threat memories, and previous studies on the role of sleep in threat generalization have produced mixed results.

Effects of COVID-19 on Blood Culture Contamination at a Tertiary Care Academic Medical Center.

The COVID-19 pandemic has changed health care, from increased needs of personal protective equipment (PPE) to overloaded staff and influxes of patients. Blood cultures are frequently used to detect bloodstream infections in critically ill patients, but it is unknown whether the COVID-19 pandemic has had an impact on blood culture contamination rates. A total of 88,332 blood cultures taken over a 33-month period were analyzed to compare blood culture contamination rates before the COVID-19 pandemic to rates during the pandemic.

Expression of IGF-2 Receptor in the Auditory Cortex Improves the Precision of Recent Fear Memories and Maintains Detailed Remote Fear Memories Over Time.

Traumatic memories may become less precise over time and lead to the development of fear responses to novel stimuli, a process referred to as time-dependent fear generalization. The conditions that cause the growth of fear generalization over time are poorly understood. Here, we found that, in male rats, the level of discrimination at the early time point contributes to determining whether fear generalization will develop with the passage of time or not, suggesting a link between the precision of recent memory and the stability of remote engrams.

Implicit and explicit systems differently predict possible dangers.

One strategy to address new potential dangers is to generate defensive responses to stimuli that remind learned threats, a phenomenon called fear generalization. During a threatening experience, the brain encodes implicit and explicit memory traces. Nevertheless, there is a lack of studies comparing implicit and explicit response patterns to novel stimuli.

The Potential Role of Quorum Sensing in Clonal Growth and Subsequent Expansion of Bone Marrow Stromal Cell Strains in Culture.

Clonal development (clonogenicity) is an inherent property of a subset of postnatal bone marrow (BM) adherent stromal mesenchymal stem cells (MSCs) from which a multipotent progeny develops in culture. Our data suggest that clonogenicity and BM-MSC expansion are two distinct biological events. This hypothesis is based on the following observations: (1) the beginning of clonal growth is a property strictly dependent on serum and independent of the social context, (2) the expansion of individual clone is influenced by events deriving from a social context during initial growth, (3) clonogenic cells grown in a social context in presence of serum can emancipate themselves to generate a secondary different progeny, and (4) the ability of socially generated clones to develop an inherent potential for further growth suggests that quorum sensing may operate in BM-MSC cultures and determine the potential growth of clonal strains.

Human Sinusoidal Subendothelial Cells Regulate Homing and Invasion of Circulating Metastatic Prostate Cancer Cells to Bone Marrow.

Subendothelial cells (pericytes) are the clonogenic, multipotent and self-renewing skeletal stem cells (SSCs) found in bone marrow (BM) stroma. They express genes maintaining hematopoietic stem cell (HMC) niche identity and, transplanted in immunocompromised mice, organize the hematopoietic microenvironment (HME) generating humanized bone/BM ossicles. To create a mouse model of hematogenous metastasis of human prostate cancer (PC) cells to human bone/BM, we injected PC cells in the blood circulatory system of Severe Combined Immunodeficiency (SCID)/beige mice bearing heterotopic ossicles.

CAR-T with License to Kill Solid Tumors in Search of a Winning Strategy.

Artificial receptors designed for adoptive immune therapies need to absolve dual functions: antigen recognition and abilities to trigger the lytic machinery of reprogrammed effector T lymphocytes. In this way, CAR-T cells deliver their cytotoxic hit to cancer cells expressing targeted tumor antigens, bypassing the limitation of HLA-restricted antigen recognition. Expanding technologies have proposed a wide repertoire of soluble and cellular "immunological weapons" to kill tumor cells; they include monoclonal antibodies recognizing tumor associated antigens on tumor cells and immune cell checkpoint inhibition receptors expressed on tumor specific T cells.

Corrigendum: 3D hydrogel environment rejuvenates aged pericytes for skeletal muscle tissue engineering.

[This corrects the article DOI: 10.3389/fphys.2014.

The auditory cortex and the emotional valence of sounds.

How and where sensory stimuli, such as tones or lights, are linked to valence is an important unresolved question in the field of neuroscience. The auditory cortex is essential to analyse the identity and the behavioural importance of tones paired with emotional events. On the contrary, whether the auditory cortex may also encode information on the emotional-motivational valence of sounds is much more controversial.

Coherent Activity between the Prelimbic and Auditory Cortex in the Slow-Gamma Band Underlies Fear Discrimination.

The medial prefrontal cortex and the basolateral amygdala (BLA) are essential for discriminating between harmful and safe stimuli. The primary auditory cortex (Te1) sends projections to both sites, but whether and how it interacts with these areas during fear discrimination are poorly understood. Here we show that in male rats that can differentiate between a new tone and a threatening one, the selective optogenetic inhibition of Te1 axon terminals into the prelimbic (PL) cortex shifted discrimination to fear generalization.

Clonal Analysis Delineates Transcriptional Programs of Osteogenic and Adipogenic Lineages of Adult Mouse Skeletal Progenitors.

Bone, cartilage, and marrow adipocytes are generated by skeletal progenitors, but the relationships between lineages and mechanisms controlling their differentiation are poorly understood. We established mouse clonal skeletal progenitors with distinct differentiation properties and analyzed their transcriptome. Unipotent osteogenic and adipogenic cells expressed specific transcriptional programs, whereas bipotent clones combined expression of those genes and did not show a unique signature.

A neuronal basis for fear discrimination in the lateral amygdala.

In the presence of new stimuli, it is crucial for survival to react with defensive responses in the presence of stimuli that resemble threats but also to not react with defensive behavior in response to new harmless stimuli. Here, we show that in the presence of new uncertain stimuli with sensory features that produce an ambiguous interpretation, discriminative processes engage a subset of excitatory and inhibitory neurons within the lateral amygdala (LA) that are partially different from those engaged by fear processes. Inducing the pharmacogenetic deletion of this neuronal ensemble caused fear generalization but left anxiety-like response, fear memory and extinction processes intact.

CAR-T cells: the long and winding road to solid tumors.

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses.

Lateral and Basal Amygdala Account for Opposite Behavioral Responses during the Long-Term Expression of Fearful Memories.

Memories of fearful events can be maintained throughout the lifetime of animals. Here we showed that lesions of the lateral nucleus (LA) performed shortly after training impaired the retention of long-term memories, assessed by the concomitant measurement of two dissociable defensive responses, freezing and avoidance in rats. Strikingly, when LA lesions were performed four weeks after training, rats did not show freezing to a learned threat stimulus, but they were able to direct their responses away from it.

Effect of miR-204&211 and RUNX2 control on the fate of human mesenchymal stromal cells.

MiR-204 and 211 enforced expression in murine mesenchymal stromal cells (MSCs) has been shown to induce adipogenesis and impair osteogenesis, through RUNX2 down-modulation. This mechanism has been suggested to play a role in osteoporosis associated with obesity. However, two further fundamental MSC functions, chondrogenesis and hematopoietic supporting activity, have not yet been explored.

Clonogenic, myogenic progenitors expressing MCAM/CD146 are incorporated as adventitial reticular cells in the microvascular compartment of human post-natal skeletal muscle.

Recent observation identifies subendothelial (mural) cells expressing MCAM, a specific system of clonogenic, self-renewing, osteoprogenitors (a.k.a, "mesenchymal stem cells") in the microvascular compartment of post-natal human bone marrow (BM).

The angiogenic properties of human adipose-derived stem cells (HASCs) are modulated by the High mobility group box protein 1 (HMGB1).

Peripheral arterial disease (PAD), is a major health problem. Many studies have been focused on the possibilities of treatment offered by vascular regeneration. Human adipose-derived stem cells (HASCs), multipotent CD34+ stem cells found in the stromal-vascular fraction of adipose tissues, which are capable to differentiate into multiple mesenchymal cell types.

Reversible Inactivation of the Higher Order Auditory Cortex during Fear Memory Consolidation Prevents Memory-Related Activity in the Basolateral Amygdala during Remote Memory Retrieval.

Recent findings have shown that the auditory cortex, and specifically the higher order Te2 area, is necessary for the consolidation of long-term fearful memories and that it interacts with the amygdala during the retrieval of long-term fearful memories. Here, we tested whether the reversible blockade of Te2 during memory consolidation may affect the activity changes occurring in the amygdala during the retrieval of fearful memories. To address this issue, we blocked Te2 in a reversible manner during memory consolidation processes.