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1.
Sci Adv ; 10(28): eadk3365, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38985873

ABSTRACT

It remains unexplored in the field of fear memory whether functional neuronal connectivity between two brain areas is necessary for one sex but not the other. Here, we show that chemogenetic silencing of centromedial (CeM)-Tac2 fibers in the lateral posterior BNST (BNSTpl) decreased fear memory consolidation in male mice but not females. Optogenetic excitation of CeM-Tac2 fibers in the BNSTpl exhibited enhanced inhibitory postsynaptic currents in males compared to females. In vivo calcium imaging analysis revealed a sex-dimorphic fear memory engram in the BNSTpl. Furthermore, in humans, the single-nucleotide polymorphism (SNP) in the Tac2 receptor (rs2765) (TAC3R) decreased CeM-BNST connectivity in a fear task, impaired fear memory consolidation, and increased the expression of the TAC3R mRNA in AA-carrier men but not in women. These sex differences in critical neuronal circuits underlying fear memory formation may be relevant to human neuropsychiatric disorders with fear memory alterations such as posttraumatic stress disorder.


Subject(s)
Fear , Memory , Sex Characteristics , Fear/physiology , Animals , Female , Male , Humans , Mice , Memory/physiology , Polymorphism, Single Nucleotide , Adult
2.
NAR Genom Bioinform ; 6(3): lqae075, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39022326

ABSTRACT

The Catalan Initiative for the Earth BioGenome Project (CBP) is an EBP-affiliated project network aimed at sequencing the genome of the >40 000 eukaryotic species estimated to live in the Catalan-speaking territories (Catalan Linguistic Area, CLA). These territories represent a biodiversity hotspot. While covering less than 1% of Europe, they are home to about one fourth of all known European eukaryotic species. These include a high proportion of endemisms, many of which are threatened. This trend is likely to get worse as the effects of global change are expected to be particularly severe across the Mediterranean Basin, particularly in freshwater ecosystems and mountain areas. Following the EBP model, the CBP is a networked organization that has been able to engage many scientific and non-scientific partners. In the pilot phase, the genomes of 52 species are being sequenced. As a case study in biodiversity conservation, we highlight the genome of the Balearic shearwater Puffinus mauretanicus, sequenced under the CBP umbrella.

3.
Behav Res Ther ; 178: 104548, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38704974

ABSTRACT

It is still unclear how the human brain consolidates aversive (e.g., traumatic) memories and whether this process can be disrupted. We hypothesized that the dorsolateral prefrontal cortex (dlPFC) is crucially involved in threat memory consolidation. To test this, we used low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) within the memory stabilization time window to disrupt the expression of threat memory. We combined a differential threat-conditioning paradigm with LF-rTMS targeting the dlPFC in the critical condition, and occipital cortex stimulation, delayed dlPFC stimulation, and sham stimulation as control conditions. In the critical condition, defensive reactions to threat were reduced immediately after brain stimulation, and 1 h and 24 h later. In stark contrast, no decrease was observed in the control conditions, thus showing both the anatomical and temporal specificity of our intervention. We provide causal evidence that selectively targeting the dlPFC within the early consolidation period prevents the persistence and return of conditioned responses. Furthermore, memory disruption lasted longer than the inhibitory window created by our TMS protocol, which suggests that we influenced dlPFC neural activity and hampered the underlying, time-dependent consolidation process. These results provide important insights for future clinical applications aimed at interfering with the consolidation of aversive, threat-related memories.


Subject(s)
Dorsolateral Prefrontal Cortex , Fear , Memory Consolidation , Transcranial Magnetic Stimulation , Humans , Transcranial Magnetic Stimulation/methods , Male , Memory Consolidation/physiology , Female , Young Adult , Adult , Fear/psychology , Fear/physiology , Dorsolateral Prefrontal Cortex/physiology , Conditioning, Classical/physiology , Prefrontal Cortex/physiology
4.
Sci Total Environ ; 935: 173243, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-38761946

ABSTRACT

Determining biological status of freshwater ecosystems is critical for ensuring ecosystem health and maintaining associated services to such ecosystems. Freshwater macroinvertebrates respond predictably to environmental disturbances and are widely used in biomonitoring programs. However, many freshwater species are difficult to capture and sort from debris or substrate and morphological identification is challenging, especially larval stages, damaged specimens, or hyperdiverse groups such as Diptera. The advent of high throughput sequencing technologies has enhanced DNA barcoding tools to automatise species identification for whole communities, as metabarcoding is increasingly used to monitor biodiversity. However, recent comparisons have revealed little congruence between morphological and molecular-based identifications. Using broad range universal primers for DNA barcode marker cox1, we compare community composition captured between morphological and molecular-based approaches from different sources - tissue-based (bulk benthic and bulk drift samples) and environmental DNA (eDNA, filtered water) metabarcoding - for samples collected along a gradient of anthropogenic disturbances. For comparability, metabarcoding taxonomic assignments were filtered by taxa included in the standardised national biological metric IBMWP. At the family level, bulk benthic metabarcoding showed the highest congruence with morphology, and the most abundant taxa were captured by all techniques. Richness captured by morphology and bulk benthic metabarcoding decreased along the gradient, whereas richness recorded by eDNA remained constant and increased downstream when sequencing bulk drift. Estimates of biological metrics were higher using molecular than morphological identification. At species level, diversity captured by bulk benthic samples were higher than the other techniques. Importantly, bulk benthic and eDNA metabarcoding captured different and complementary portions of the community - benthic versus water column, respectively - and their combined use is recommended. While bulk benthic metabarcoding can likely replace morphology using similar benthic biological indices, water eDNA will require new metrics because this technique sequences a different portion of the community.


Subject(s)
Biodiversity , DNA Barcoding, Taxonomic , Environmental Monitoring , Fresh Water , Invertebrates , Animals , Invertebrates/genetics , Invertebrates/classification , Environmental Monitoring/methods , DNA, Environmental , Ecosystem , Biological Monitoring/methods
6.
Nat Struct Mol Biol ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38632359

ABSTRACT

Current models suggest that DNA double-strand breaks (DSBs) can move to the nuclear periphery for repair. It is unclear to what extent human DSBs display such repositioning. Here we show that the human nuclear envelope localizes to DSBs in a manner depending on DNA damage response (DDR) kinases and cytoplasmic microtubules acetylated by α-tubulin acetyltransferase-1 (ATAT1). These factors collaborate with the linker of nucleoskeleton and cytoskeleton complex (LINC), nuclear pore complex (NPC) protein NUP153, nuclear lamina and kinesins KIF5B and KIF13B to generate DSB-capturing nuclear envelope tubules (dsbNETs). dsbNETs are partly supported by nuclear actin filaments and the circadian factor PER1 and reversed by kinesin KIFC3. Although dsbNETs promote repair and survival, they are also co-opted during poly(ADP-ribose) polymerase (PARP) inhibition to restrain BRCA1-deficient breast cancer cells and are hyper-induced in cells expressing the aging-linked lamin A mutant progerin. In summary, our results advance understanding of nuclear structure-function relationships, uncover a nuclear-cytoplasmic DDR and identify dsbNETs as critical factors in genome organization and stability.

7.
Neurosci Biobehav Rev ; 161: 105678, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38621516

ABSTRACT

Family accommodation might play a crucial role in obsessive-compulsive disorder (OCD). Previous systematic reviews on family accommodation in OCD have focused on specific populations or variables or are outdated. We conducted a preregistered systematic review and meta-analysis on family accommodation in adults, children, and adolescents with OCD (CRD42021264461). We searched PubMed, Scopus, and Web of Science using the keywords "family accommodation" and "obsessive-compulsive disorder. One hundred-eight studies involving 8928 individuals with OCD were included. Our results indicate that levels of family accommodation in OCD are moderate, that there is a significant positive correlation between family accommodation and OCD severity (r = 0.42), that baseline family accommodation does not predict pre- to post-treatment change in OCD severity (g = -0.03), and that family accommodation decreases as a result of both individual and family-focused cognitive behavioral therapy for OCD (g = 2.00 and g = 1.17, respectively). Our findings highlight the relevance of family accommodation in OCD and may help guide assessment and treatment.


Subject(s)
Family , Obsessive-Compulsive Disorder , Obsessive-Compulsive Disorder/physiopathology , Obsessive-Compulsive Disorder/therapy , Humans , Family/psychology
8.
Eur Neuropsychopharmacol ; 83: 19-26, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38492550

ABSTRACT

Trait anxiety is a well-established risk factor for anxiety and depressive disorders, yet its neural correlates are not clearly understood. In this study, we investigated the neural correlates of trait anxiety in a large sample (n = 179) of individuals who completed the trait and state versions of the State-Trait Anxiety Inventory and underwent resting-state functional magnetic resonance imaging. We used independent component analysis to characterize individual resting-state networks (RSNs), and multiple regression analyses to assess the relationship between trait anxiety and intrinsic connectivity. Trait anxiety was significantly associated with intrinsic connectivity in different regions of three RSNs (dorsal attention network, default mode network, and auditory network) when controlling for state anxiety. These RSNs primarily support attentional processes. Notably, when state anxiety was not controlled for, a different pattern of results emerged, highlighting the importance of considering this factor in assessing the neural correlates of trait anxiety. Our findings suggest that trait anxiety is uniquely associated with resting-state brain connectivity in networks mainly supporting attentional processes. Moreover, controlling for state anxiety is crucial when assessing the neural correlates of trait anxiety. These insights may help refine current neurobiological models of anxiety and identify potential targets for neurobiologically-based interventions.


Subject(s)
Anxiety , Attention , Brain , Magnetic Resonance Imaging , Nerve Net , Humans , Male , Female , Anxiety/psychology , Anxiety/physiopathology , Attention/physiology , Adult , Young Adult , Brain/diagnostic imaging , Brain/physiopathology , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Brain Mapping , Adolescent , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging
9.
Mov Disord ; 39(6): 1054-1059, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38470080

ABSTRACT

BACKGROUND: Isolated Rapid Eye Movement (REM) sleep Behavior Disorder (iRBD) requires quantitative tools to detect incipient Parkinson's disease (PD). METHODS: A motor battery was designed and compared with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III) in people with iRBD and controls. This included two keyboard-based tests (BRadykinesia Akinesia INcoordination tap test and Distal Finger Tapping) and two dual tasking tests (walking and finger tapping). RESULTS: We included 33 iRBD patients and 29 controls. The iRBD group performed both keyboard-based tapping tests more slowly (P < 0.001, P = 0.020) and less rhythmically (P < 0.001, P = 0.006) than controls. Unlike controls, the iRBD group increased their walking duration (P < 0.001) and had a smaller amplitude (P = 0.001) and slower (P = 0.007) finger tapping with dual task. The combination of the most salient motor markers showed 90.3% sensitivity for 89.3% specificity (area under the ROC curve [AUC], 0.94), which was higher than the MDS-UPDRS-III (minus action tremor) (69.7% sensitivity, 72.4% specificity; AUC, 0.81) for detecting motor dysfunction. CONCLUSION: Speed, rhythm, and dual task motor deterioration might be accurate indicators of incipient PD in iRBD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Subject(s)
Parkinson Disease , REM Sleep Behavior Disorder , Humans , REM Sleep Behavior Disorder/physiopathology , REM Sleep Behavior Disorder/diagnosis , Male , Female , Aged , Middle Aged , Parkinson Disease/physiopathology , Parkinson Disease/complications , Psychomotor Performance/physiology , Walking/physiology , Severity of Illness Index
10.
Angew Chem Int Ed Engl ; 63(9): e202315872, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38093613

ABSTRACT

Asymmetric hydrogenation (AH) of tetrasubstituted olefins generating two stereocenters is still an open topic. There are only a few reports on the AH of tetrasubstituted olefins with conjugated functional groups, while this process can create useful intermediates for the subsequent elaboration of relevant end products. Most of the tetrasubstituted olefins successfully submitted to AH belong to a small number of functional classes; remarkably, the AH of tetrasubstituted acyclic enones still represents an unsolved challenge. Herein, we disclose a class of air-stable Ir-P,N catalysts, prepared in three steps from commercially available amino alcohols, that can hydrogenate, in minutes, a wide range of electronically and sterically diverse acyclic tetrasubstituted enones (including exocyclic ones) with high yields and high enantioselectivities. The factors responsible for the excellent selectivities were elucidated by combining deuterogenation experiments and theoretical calculations. The calculations indicated that the reduction follows an IrI /IrIII mechanism, in which enantioselectivity is controlled in the first migratory insertion of the hydride to the most electrophilic olefinic Cß and the formation of the hydrogenated product via reductive elimination takes place prior to the coordination of dihydrogen and the subsequent oxidative addition. The potential of the new catalytic systems is demonstrated by the derivatization of hydrogenation products.

11.
Sci Total Environ ; 912: 169561, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38142994

ABSTRACT

The use of urban wastewater reclaimed water has recently increased across the globe to restore stream environmental flows and mitigate the effects of water scarcity. Reclaimed water is disinfected using different treatments, but their effects into the receiving rivers are little studied. Physiological bioassays and biomarkers can detect sub-lethal effects on target species, but do not provide information on changes in community structure. In contrast, official monitoring programs use community structure information but often at coarse taxonomic resolution level that may fail to detect species level impacts. Here, we combined commonly used biomonitoring approaches from organism physiology to community species composition to scan a broad range of effects of disinfection of reclaimed water by UV-light only and both UV/chlorine on the biota. We (1) performed bioassays in one laboratory species (water flea Daphnia magna) and measured biomarkers in two wild species (caddisfly Hydropsyche exocellata and the barbel Luciobarbus graellsii), (2) calculated standard indices of biotic quality (IBQ) for diatoms, benthic macroinvertebrates, and fishes, and (3) analysed community species composition of eukaryotes determined by Cytochrome Oxidase C subunit I (cox1) metabarcoding. Only the UV/chlorine treatment caused significant changes in feeding rates of D. magna and reduced antioxidant defenses, increased anaerobic metabolism and altered the levels of lipid peroxidiation in H. exocellata. However, inputs of reclaimed water were significantly associated with a greater proportion of circulating neutrophils and LG-PAS cells in L. graellsii. Despite IBQ did not discriminate between the two water treatments, metabarcoding data detected community composition changes upon exposure to UV/chlorine reclaimed water. Overall, despite the effects of UV/chlorine-treated water were transient, our study suggests that UV-light treated is less harmful for freshwater biota than UV/chlorine-treated reclaimed water, but those effects depend of the organizational level.


Subject(s)
Wastewater , Water Purification , Animals , Chlorine/chemistry , Insecta , Disinfection , Chlorides , Biota , Rivers
12.
Int J Integr Care ; 23(4): 18, 2023.
Article in English | MEDLINE | ID: mdl-38107836

ABSTRACT

Introduction: The evaluation of integrated care programmes for high-need high-cost older people is a challenge. We aim to share the early implementation results of the ProPCC programme in the North-Barcelona metropolitan area, in Catalonia, Spain. Methods: We analysed the intervention with retrospective data from May 2018 to December 2021 by describing the cohort complexity and by showing its 6-months pre-post impact on time spent at home and resources used: primary care visits, emergency department visits, hospital admissions and hospital stay. Findings: 264 cases were included (91% at home; 9% in nursing homes). 6-month pre vs. 6-months post results were (mean, p-value): primary care visits 8.2 vs. 11.5 (p < 0.05); emergency department visits 1.4 vs. 0.9 (p < 0.05); hospital admissions 0.7 vs. 0.5 (p < 0.05); hospital stay 12.8 vs. 7.9 days (p < 0.05). Time spent at home was 169.2 vs.174.2 days (p < 0.05). Conclusion: Early implementation of the ProPCC programme results in an increase in time spent at home (up to 3%) and significant reductions in emergency department attendance (-37.2%) and hospital stays (-38.3%). The increased use of primary care resources is compensated by the hospital resources savings, with a result in the average total cost of -46.3%.

13.
Cell Rep ; 42(10): 113256, 2023 10 31.
Article in English | MEDLINE | ID: mdl-37847590

ABSTRACT

It is widely assumed that all normal somatic cells can equally perform homologous recombination (HR) and non-homologous end joining in the DNA damage response (DDR). Here, we show that the DDR in normal mammary gland inherently depends on the epithelial cell lineage identity. Bioinformatics, post-irradiation DNA damage repair kinetics, and clonogenic assays demonstrated luminal lineage exhibiting a more pronounced DDR and HR repair compared to the basal lineage. Consequently, basal progenitors were far more sensitive to poly(ADP-ribose) polymerase inhibitors (PARPis) in both mouse and human mammary epithelium. Furthermore, PARPi sensitivity of murine and human breast cancer cell lines as well as patient-derived xenografts correlated with their molecular resemblance to the mammary progenitor lineages. Thus, mammary epithelial cells are intrinsically divergent in their DNA damage repair capacity and PARPi vulnerability, potentially influencing the clinical utility of this targeted therapy.


Subject(s)
Antineoplastic Agents , Poly(ADP-ribose) Polymerase Inhibitors , Humans , Animals , Mice , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Antineoplastic Agents/pharmacology , DNA Repair , Homologous Recombination , DNA Damage
14.
ACS Sustain Chem Eng ; 11(12): 4885-4893, 2023 Mar 27.
Article in English | MEDLINE | ID: mdl-37869721

ABSTRACT

A commercially available Lipase B from Candida antarctica immobilized onto a macroporous support (Novozym 435) has been employed in the presence of H2O2 as a benign oxidant for the epoxidation of various biorenewable terpenes. This epoxidation protocol was explored under both heterogeneous batch and continuous flow conditions. The catalyst recyclability was also investigated demonstrating good activity throughout 10 cycles under batch conditions, while the same catalyst system could also be productively used under continuous flow operation for more than 30 h. This practical and relatively safe sustainable flow epoxidation of di- and trisubstituted alkenes by H2O2 allows for the production of gram quantities of a range of terpene epoxides. As a proof of principle, the same protocol can also be applied to the epoxidation of biobased polymers as a means to post-functionalize these macromolecules and equip them with cross-linkable epoxy groups.

16.
ACS Catal ; 13(1): 706-713, 2023 Jan 06.
Article in English | MEDLINE | ID: mdl-37808365

ABSTRACT

In the context of copper-catalyzed nitrene transfer to olefins, many systems operate upon mixing a CuX salt (X = halide, OTf) and a polydentate N-based ligand, assuming that the X ligand is displaced from the coordination sphere toward a counterion position. Herein, we demonstrated that such general assumption should be in doubt since studies carried out with the well-defined copper(I) complexes (TTM)CuCl and [(TTM)Cu(NCMe)]PF6 (TTM = tris(triazolyl)methane ligand) demonstrate a dual behavior from a catalytic and mechanistic point of view that exclusively depends on the presence or absence of the chloride ligand bonded to the metal center. When coordinated, the turnover-limiting step corresponds to the formation of the carbon-nitrene bond, whereas in its absence, the highest barrier corresponds to the formation of the copper-nitrene intermediate.

17.
Plants (Basel) ; 12(20)2023 Oct 12.
Article in English | MEDLINE | ID: mdl-37896015

ABSTRACT

Salinity is a major stress factor that compromises vegetable production in semi-arid climates such as the Mediterranean. The accumulation of salts in the soil can be attributed to limited water availability, which can be exacerbated by changes in rainfall patterns and rising temperatures. These factors can alter soil moisture levels and evaporation rates, ultimately leading to an increase in soil salinity, and, concomitantly, the extent to which crop yield is affected by salinity stress is considered cultivar-dependent. In contrast to tomato hybrids, tomato landraces often exhibit greater genetic diversity and resilience to environmental stresses, constituting valuable resources for breeding programs seeking to introduce new tolerance mechanisms. Therefore, in the present study, we investigated the effects of mild salinity stress on the growth, yield, and nutritional status of sixteen Mediterranean tomato landraces of all size types that had been pre-selected as salinity tolerant in previous screening trials. The experiment was carried out in the greenhouse facilities of the Laboratory of Vegetable Production at the Agricultural University of Athens. To induce salinity stress, plants were grown hydroponically and irrigated with a nutrient solution containing NaCl at a concentration that could maintain the NaCl level in the root zone at 30 mM, while the non-salt-treated plants were irrigated with a nutrient solution containing 0.5 mM NaCl. Various plant growth parameters, including dry matter content and fruit yield (measured by the number and weight of fruits per plant), were evaluated to assess the impact of salinity stress. In addition, the nutritional status of the plants was assessed by determining the concentrations of macro- and micronutrients in the leaves, roots, and fruit of the plants. The key results of this study reveal that cherry-type tomato landraces exhibit the highest tolerance to salinity stress, as the landraces 'Cherry-INRAE (1)', 'Cherry-INRAE (3)', and 'Cherry-INRAE (4)' did not experience a decrease in yield when exposed to salinity stress. However, larger landraces such as 'de Ramellet' also exhibit mechanisms conferring tolerance to salinity, as their yield was not compromised by the stress applied. The identified tolerant and resistant varieties could potentially be used in breeding programs to develop new varieties and hybrids that are better adapted to salinity-affected environments. The identification and utilization of tomato varieties that are adapted to salinity stress is an important strategy for promoting agriculture sustainability, particularly in semi-arid regions where salinity stress is a major challenge.

18.
Bioorg Med Chem Lett ; 93: 129412, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37499987

ABSTRACT

Small-molecule capsid assembly modulators (CAMs) have been recently recognized as promising antiviral agents for curing chronic hepatitis B virus (HBV) infection. A target-based in silico screening study is described, aimed towards the discovery of novel HBV CAMs. Initial optimization of four weakly active screening hits was performed via focused library synthesis. Lead compound 42 and close analogues 56 and 57 exhibited in vitro potency in the sub- and micromolar range along with good physico-chemical properties and were further evaluated in molecular docking and mechanism of action studies.


Subject(s)
Hepatitis B, Chronic , Hepatitis B , Humans , Hepatitis B virus , Capsid , Virus Assembly , Molecular Docking Simulation , Capsid Proteins , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Virus Replication
19.
Syst Biol ; 72(5): 998-1012, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37474131

ABSTRACT

Natural selection plays a key role in deterministic evolution, as clearly illustrated by the multiple cases of repeated evolution of ecomorphological characters observed in adaptive radiations. Unlike most spiders, Dysdera species display a high variability of cheliceral morphologies, which has been suggested to reflect different levels of specialization to feed on isopods. In this study, we integrate geometric morphometrics and experimental trials with a fully resolved phylogeny of the highly diverse endemic species from the Canary Islands to 1) quantitatively delimit the different cheliceral morphotypes present in the archipelago, 2) test their association with trophic specialization, as reported for continental species, 3) reconstruct the evolution of these ecomorphs throughout the diversification of the group, 4) test the hypothesis of convergent evolution of the different morphotypes, and 5) examine whether specialization constitutes a case of evolutionary irreversibility in this group. We show the existence of 9 cheliceral morphotypes and uncovered their significance for trophic ecology. Further, we demonstrate that similar ecomorphs evolved multiple times in the archipelago, providing a novel study system to explain how convergent evolution and irreversibility due to specialization may be combined to shape phenotypic diversification in adaptive radiations.


Subject(s)
Biological Evolution , Spiders , Animals , Phylogeny , Spain , Ecology
20.
Neurosci Biobehav Rev ; 152: 105308, 2023 09.
Article in English | MEDLINE | ID: mdl-37419231

ABSTRACT

Pathological fear and anxiety are a leading cause of human misery and morbidity, afflicting millions of individuals worldwide. Yet existing treatments are inconsistently effective or associated with significant adverse effects, underscoring the urgency of developing a more complete understanding of the neural systems governing fear and anxiety in humans. This emphasis reflects the fact that fear and anxiety disorders are defined and diagnosed based on subjective symptoms, and human studies are essential for understanding the neural mechanisms that underlie the experience of fear and anxiety. Human studies are also crucial for identifying the features of animal models that are conserved and, hence, most relevant to human disease and treatment development ('forward translation'). Finally, human studies afford opportunities for developing objective biomarkers of disease or disease risk, accelerating the development of new diagnostic and treatment strategies, and generating novel hypotheses that can be mechanistically assessed in animal models ('reverse translation'). The present Special Issue-The Neurobiology of Human Fear and Anxiety-provides a concise survey of recent progress in this burgeoning area of research. Here we provide an Introduction to the Special Issue, highlighting some of the most significant and exciting advances.


Subject(s)
Anxiety , Fear , Animals , Humans , Anxiety Disorders , Brain , Models, Animal
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