A population of immature cerebellar parallel fibre synapses are insensitive to adenosine but are inhibited by hypoxia

The purine adenosine plays an important role in a number of physiological and pathological processes and is neuroprotective during hypoxia and ischemia. The major effect of adenosine is to suppress network activity via the activation of A1 receptors. Here we report that in immature cerebellar slices, the activation of A1 receptors has variable effects on parallel fibre synaptic transmission, ranging from zero depression to an almost complete abolition of transmission. Concentration–response curves suggest that the heterogeneity of inhibition stems from differences in A1 receptor properties which could include coupling to downstream effectors. There is less variation in the effects of adenosine at parallel fibre synapses in slices from older rats and thus adenosine signalling appears developmentally regulated. In the cerebellum, hypoxia increases the concentration of extracellular adenosine leading to the activation of A1 receptors (at adenosine-sensitive parallel fibre synapses) and the suppression of glutamate release. It would be predicted that the synapses that were insensitive to adenosine would be less depressed by hypoxia and thus maintain function during metabolic stress. However those synapses which were insensitive to adenosine were rapidly inhibited by hypoxia via a mechanism which was not reversed by blocking A1 receptors. Thus another mechanism must be responsible for the hypoxia-mediated depression at these synapses. These different mechanisms of depression may be important for cell survival and for maintenance of cerebellar function following oxygen starvation

Employment Protection and Domestic Violence: Addressing Abuse in the Labor Grievance Process

The effects of domestic violence are not limited to the home environment. Its effects are felt in employment when abused employees are absent from work and when violent incidents erupt in the workplace. For example, a bruised employee might be too injured and embarrassed to attend work, or an estranged spouse might stalk and harass a victim on the job. Another issue arises in that employers often discipline victims of domestic violence for absenteeism and incidents of violence that occur in the workplace. Discipline of union members is governed by collective bargaining agreements and subject to the labor grievance process. These grievances often end in arbitration, where the union represents the battered employee. Because of this occurrence, employers, unions, and arbitrators must be educated about domestic violence to ensure victims of abuse receive adequate job protection

Adaptations: Blood and All You Zombies

The author describes the experience of adapting two different short stories for the stage, one as a solo playwright and one as part of an ensemble performance workshop

Development of adenosine signalling in the cerebellum

The release and clearance of adenosine are reasonably well-documented in the mature CNS but relatively little is known about how adenosine signalling changes during postnatal development. The activation of presynaptic A1 receptors (A1R) at cerebellar parallel fibre terminals is known to inhibit synaptic transmission and the expression of A1R has been observed in mature rat cerebellar slices. However its distribution during development or in relation to parallel fibre–Purkinje cell (PF-PC) synapses has not previously been described. In the mature cerebellum blockade of presynaptic A1R at PF-PC synapses enhances synaptic transmission suggesting an inhibitory adenosine tone and an extracellular purine tone is detectable with microelectrode biosensors under basal conditions. The active release of adenosine can be stimulated with trains of activity in the molecular layer of mature slices although this does not appear to be a source of the basal extracellular adenosine tone. This study used immunohistochemistry to determine the distribution of A1R at PFPC synapses in cerebellar slices at postnatal day 3 prior to PF-PC synapse formation, postnatal days 8-14 and postnatal days 21-28. This study also used cerebellar slices from rats at postnatal days 9-14 to investigate the pharmacological profile of the immature rat PF-PC synapse with electrophysiology and microelectrode biosensors. The immunohistochemistry suggests that A1R are widely distributed across Purkinje cell bodies and their dendrites and within the granule layer of the cerebellum and that its expression does not change during development. The same staining patterns were also observed prior to PF-PC synapse formation. Application of adenosine resulted in a variable A1R-mediated inhibition at immature PF-PC synapses. This did not appear to be gender-specific or correlated with age of rat and the synapses otherwise appeared identical in their properties. The comparison of log concentration-response curves generated for an A1R agonist suggested that some A1R may have a lower efficacy at this stage of development. Blockade of presynaptic A1R at immature PF-PC synapses suggested that an inhibitory adenosine tone is low or absent at this stage of development and is not the result of a low A1R expression or developmental differences in A1R efficacy. Inhibition of adenosine clearance via adenosine deaminase, adenosine kinase and equilibrative transporters had little effect on synaptic transmission suggesting that little adenosine is moving between the intracellular and extracellular spaces under basal conditions in immature slices. Active adenosine release measured by electrophysiology and microelectrode biosensors could be stimulated with hypoxia in immature slices but this was delayed and slower in comparison to the release observed in mature slices. Adenosine could not be actively released at immature PFPC synapses in response to electrical stimulation in the molecular layer

The Snowball Effect - Why the U.S. Gets Knocked Out Cold in Vietnam and Afghanistan

Since the late 1940s, the United States (U.S.) has made several attempts at nation-building, defined as U.S. political, economic, and military intervention into a foreign country with the intent of establishing a pro-U.S. government or democracy. Many Americans associate nation-building with catastrophic failure, largely due to Vietnam in 1975 and Afghanistan in 2021. The primary reason for the U.S.\u27 failure to nation-build was the lack of political and public support, both from the populations of the U.S. at home, and the native Vietnamese / Afghani populations. Growing resentment, or lack of interest in the war effort destroyed American morale, creating a desire to quickly end the conflict. When combined with disorganized military and political objectives, as well as a lack of cultural understanding of Vietnam / Afghanistan on the part of the Americans, it becomes clear why both these efforts ended in catastrophe, and the desperate evacuation of civilians from the U.S. embassy in Saigon in 1975, or Kabul in 2021

Veterinary use of bacteriophage therapy in intensively-reared livestock

Zoonoses are infectious diseases transmitted directly or indirectly between animals and humans. Several important zoonotic pathogens colonize farm animals asymptomatically, which may lead to contamination of the food chain and public health hazards. Moreover, routine sampling of carcasses at retail by government authorities over the past 20 years suggests the prevalence of antibiotic resistance in foodborne pathogens has increased. If this continues, antibiotics may be ineffective against such pathogens in the future and alternative approaches, such as phage therapy, may be necessary. Intensive livestock farming is the only realistic way of meeting the demand for meat from an increasing global population and growth in middle class consumers in developing countries, particularly in Asia. This review elaborates on the use of phages to control zoonotic pathogens in intensively-reared livestock (poultry and pigs)

Method for bacteriophage isolation against target Campylobacter strains

Aims: Poultry meat is considered a major source of Campylobacter. This micro-aerobic bacterium is commonly responsible for foodborne illness. This work focuses on the isolation of Campylobacter coli lytic bacteriophages (phages) against target C. coli strains. Methods and Results: A method involving the enrichment of free-range chicken samples in a broth containing the target C. coli strains and salts (CaCl2 and MgSO4) was used for phage isolation. This method allowed the isolation of 43 phages that were active against 83% of the C. coli strains used in the isolation procedure. Approximately 65% of the phages were also effective against Campylobacter jejuni strains. Conclusions: The use of target pathogens in the phage isolation step improves the likelihood of detecting and isolating phages for the control of these specific strains. Significance and Impact of the Study: This technique will be valuable in the context of phage therapy for enriching for phages that are active against specifically identified strains of bacteria, for example from a food poisoning outbreak or epidemic strains resistant to multiple antibiotics. In these situations, using the conventional methods for searching for bacteriophages active for these particular strains can be a time-consuming, if not an unsuccessful process. Using the isolation method described in this manuscript, the particular strains can be added to the enrichment broth increasing the probability of finding phages against them. Therefore, it will shorten the time needed for seeking phages able to lyse target strains, which in most of the cases, because of the rapid increase in antimicrobial-resistant bacteria, is of crucial importance.Fundação para a Ciência e a Tecnologia (FCT