Testosterone differentially modulates the display of agonistic behavior and dominance over opponents before and after adolescence in male Syrian hamsters.

The current study investigated the influence of testosterone on agonistic behavior and dominance over an opponent before and after adolescence in male Syrian hamsters (, and tested the hypothesis that shifts in behavioral responsiveness to testosterone occur across adolescent development. We predicted that testosterone-dependent modulation of attacks decreases following puberty, and that flank marking behavior in response to testosterone increases following puberty. Prepubertal (14 days of age) and adult subjects (52-62 days of age) were gonadectomized and immediately implanted with testosterone propionate (TP) or vehicle pellets.

Characterisation of resistance selection against second-/last-line antibiotics in methicillin-resistant ATCC 43300 strain.

Background And Objectives: The increasing occurrence of MRSA clinical isolates harbouring reduced susceptibility to mainstay antibiotics has escalated the use of second and last line antibiotics. Hence, it is critical to evaluate the likelihood of MRSA developing clinical resistance to these antibiotics. Our study sought to characterize the development of resistance to vancomycin (VAN), daptomycin (DAP) and linezolid (LZD) in MRSA ATCC 43300 and further determine the mechanisms underpinning resistance.

Antibiotics re-booted-time to kick back against drug resistance.

After decades of neglect and a decline in antibiotic research and development, we are now finally witnessing the advent of new funding programs dedicated to new therapies. In addition to traditional new chemical entities that directly kill or arrest the growth of bacteria, alternative approaches are being identified and advanced towards proof-of-concept trials in the clinic. We briefly review the current pipeline of conventional new antibiotics and highlight in more depth promising alternatives, including potentiators of antibiotic action, bacteriophage, lysins and microbiome modulation.

Testosterone differentially modulates the display of agonistic behavior and dominance over opponents before and after adolescence in male Syrian hamsters.

Unlabelled: The current study investigated the influence of testosterone on agonistic behavior and dominance over an opponent before and after adolescence in male Syrian hamsters ( . We hypothesized that testosterone-dependent modulation of agonistic behavior would be greater following adolescent development. To test this hypothesis, prepubertal (14 days of age) and adult subjects (52-62 days of age) were gonadectomized and immediately implanted with testosterone or vehicle pellets.

Distinguishing neural ensembles in the infralimbic cortex that regulate stress vulnerability and coping behavior.

Neural ensembles in the medial prefrontal cortex regulate several types of responses to stress. We used a Syrian hamster model to investigate the role of infralimbic (IL) neurons in coping with social defeat stress and vulnerability to subsequent anxiety-like behavior. We created social dominance relationships in male and female hamsters, used a robust activity marker (RAM) approach to label IL neural ensembles activated during social defeat stress, and employed light-dark (LD), social avoidance (SA), and conditioned defeat (CD) tests to assess anxiety-like behavior.

MacaqueNet: Advancing comparative behavioural research through large-scale collaboration.

There is a vast and ever-accumulating amount of behavioural data on individually recognised animals, an incredible resource to shed light on the ecological and evolutionary drivers of variation in animal behaviour. Yet, the full potential of such data lies in comparative research across taxa with distinct life histories and ecologies. Substantial challenges impede systematic comparisons, one of which is the lack of persistent, accessible and standardised databases.

From Play Date to Stress Fate: Juvenile Social Play Rescues Stress-Induced Changes in Adult Social Behavior.

Long-term effects of social play on neural and behavioral development remain unclear. We investigated whether just 1 h of juvenile social play could rescue the effects of play deprivation on stress-related behavior and markers of neural plasticity. Syrian hamsters were reared from postnatal days 21-43 in three conditions: peer isolation, peer isolation with daily social play sessions (dyadic play), or group-housed with littermates.

A decade of advances in human gut microbiome-derived biotherapeutics.

Microbiome science has evolved rapidly in the past decade, with high-profile publications suggesting that the gut microbiome is a causal determinant of human health. This has led to the emergence of microbiome-focused biotechnology companies and pharmaceutical company investment in the research and development of gut-derived therapeutics. Despite the early promise of this field, the first generation of microbiome-derived therapeutics (faecal microbiota products) have only recently been approved for clinical use.

Novel Macrocyclic NLRP3 Inhibitors.

Aberrant activation of NLRP3 due to persistent tissue damage, misfolded proteins or crystal deposits has been linked to multiple chronic inflammatory disorders such as cryopyrin-associated periodic syndrome (CAPS), neurodegenerative diseases, gouty arthritis, and numerous others. Hence, there has been an increasing interest in NLRP3 inhibitors as therapeutics. A first generation of NLRP3 inhibitors bearing a sulfonylurea core such as MCC950 (developed by Pfizer) were discovered by phenotypic screening, however their mode of action was only elucidated later.

Effects of social dominance and acute social stress on morphology of microglia and structural integrity of the medial prefrontal cortex.

Chronic stress increases activity of the brain's innate immune system and impairs function of the medial prefrontal cortex (mPFC). However, whether acute stress triggers similar neuroimmune mechanisms is poorly understood. Across four studies, we used a Syrian hamster model to investigate whether acute stress drives changes in mPFC microglia in a time-, subregion-, and social status-dependent manner.

Faecal microbial transfer and complex carbohydrates mediate protection against COPD.

Objective: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear.

Impact of the new membrane-targeting lipoglycopeptide antibiotic MCC5145 on the treatment of bacteremic pneumococcal pneumonia in mice.

Bacteremic pneumonia is one of the most severe forms of invasive pneumococcal disease (IPD) and with particularly high case-fatality rates among the elderly and individuals with comorbidities, exacerbated by rising antibiotic resistance and time to initiation of therapy. Here, we examined the efficacy of the preclinical "vancapticin" glycopeptide MCC5145 against fulminant infection by serotype 2 strain D39 in a bioluminescent, neutropenic mouse model of bacteremic pneumonia. MCC5145 is a semisynthetic vancomycin derivative chemically modified at the -terminus with a membrane-targeting motif designed to preferentially bind the anionic bacterial surface.

Dominance status modulates activity in medial amygdala cells with projections to the bed nucleus of the stria terminalis.

The medial amygdala (MeA) controls several types of social behavior via its projections to other limbic regions. Cells in the posterior dorsal and posterior ventral medial amygdala (MePD and MePV, respectively) project to the bed nucleus of the stria terminalis (BNST) and these pathways respond to chemosensory cues and regulate aggressive and defensive behavior. Because the BNST is also essential for the display of stress-induced anxiety, a MePD/MePV-BNST pathway may modulate both aggression and responses to stress.

Sex differences in dominance relationships in Syrian hamsters.

Dominance relationships are identified by changes in agonistic behavior toward specific individuals. While there are considerable individual and species differences in dominance relationships, sex differences are poorly understood in rodent models because aggression among female rodents is rare. The aim of this study was to characterize sex differences in the formation and maintenance of dominance relationships in same-sex pairs of male and female Syrian hamsters.

Synthesis of vancomycin fluorescent probes that retain antimicrobial activity, identify Gram-positive bacteria, and detect Gram-negative outer membrane damage.

Antimicrobial resistance is an urgent threat to human health, and new antibacterial drugs are desperately needed, as are research tools to aid in their discovery and development. Vancomycin is a glycopeptide antibiotic that is widely used for the treatment of Gram-positive infections, such as life-threatening systemic diseases caused by methicillin-resistant Staphylococcus aureus (MRSA). Here we demonstrate that modification of vancomycin by introduction of an azide substituent provides a versatile intermediate that can undergo copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction with various alkynes to readily prepare vancomycin fluorescent probes.

Purification of PaTx-II from the Venom of the Australian King Brown Snake and Characterization of Its Antimicrobial and Wound Healing Activities.

Infections caused by multi-drug-resistant (MDR) bacteria are a global threat to human health. As venoms are the source of biochemically diverse bioactive proteins and peptides, we investigated the antimicrobial activity and murine skin infection model-based wound healing efficacy of a 13 kDa protein. The active component PaTx-II was isolated from the venom of (Australian King Brown or Mulga Snake).

Comparing the ontogeny, neurobiology, and function of social play in hamsters and rats.

Syrian hamsters show complex social play behavior and provide a valuable animal model for delineating the neurobiological mechanisms and functions of social play. In this review, we compare social play behavior of hamsters and rats and underlying neurobiological mechanisms. Juvenile rats play by competing for opportunities to pin one another and attack their partner's neck.

Metal Complexes as Antifungals? From a Crowd-Sourced Compound Library to the First Experiments.

There are currently fewer than 10 antifungal drugs in clinical development, but new fungal strains that are resistant to most current antifungals are spreading rapidly across the world. To prevent a second resistance crisis, new classes of antifungal drugs are urgently needed. Metal complexes have proven to be promising candidates for novel antibiotics, but so far, few compounds have been explored for their potential application as antifungal agents.

Nitroimidazopyrazinones with Oral Activity against Tuberculosis and Chagas Disease in Mouse Models of Infection.

Tuberculosis and parasitic infections continue to impose a significant threat to global public health and economic growth. There is an urgent need to develop new treatments to combat these diseases. Here, we report the and profiles of a new bicyclic nitroimidazole subclass, namely, nitroimidazopyrazinones, against mycobacteria and .

A lipoglycopeptide antibiotic for Gram-positive biofilm-related infections.

Drug-resistant Gram-positive bacterial infections are still a substantial burden on the public health system, with two bacteria ( and ) accounting for over 1.5 million drug-resistant infections in the United States alone in 2017. In 2019, 250,000 deaths were attributed to these pathogens globally.