Artificial fluorescent sensor reveals pre-synaptic NMDA receptors switch cholecystokinin release and LTP in the hippocampus.

Cholecystokinin (CCK) has been confirmed to be essential in NMDA-dependent long-term potentiation (LTP) at mouse cortical synapses. This paper has proven that CCK is necessary for LTP induced by high-frequency stimulation of mouse hippocampal synapses projected from the entorhinal cortex. We show that the subunit of the axonal NMDA receptor dominant modulates the activity-induced LTP by triggering pre-synaptic CCK release. A functional pre-synaptic NMDA receptor is required to induce LTP mediated by the axonal Ca2+ elevation and CCK exocytosis at CCK-specific neurons. Genetic depletion of the GluN1 subunit of NMDA receptors on CCK neurons, which projected from the entorhinal cortex largely abolished the axonal Ca2+ elevation and disturbed the secretion of CCK in hippocampus. These results demonstrate that activity-induced LTP at the hippocampal synapse is CCK-dependent, and CCK secretion from the axonal terminal is modulated by pre-synaptic NMDA receptors.

The potential role of the cholecystokinin system in declarative memory.

As one of the most abundant neuropeptides in the central nervous system, cholecystokinin (CCK) has been suggested to be associated with higher brain functions, including learning and memory. In this review, we examined the potential role of the CCK system in declarative memory. First, we summarized behavioral studies that provide evidence for an important role of CCK in two forms of declarative memory-fear memory and spatial memory. Subsequently, we examined the electrophysiological studies that support the diverse roles of CCK-2 receptor activation in neocortical and hippocampal synaptic plasticity, and discussed the potential mechanisms that may be involved. Last but not least, we discussed whether the reported CCK-mediated synaptic plasticity can explain the strong influence of the CCK signaling system in neocortex and hippocampus dependent declarative memory. The available research supports the role of CCK-mediated synaptic plasticity in neocortex dependent declarative memory acquisition, but further study on the association between CCK-mediated synaptic plasticity and neocortex dependent declarative memory consolidation and retrieval is necessary. Although a direct link between CCK-mediated synaptic plasticity and hippocampus dependent declarative memory is missing, noticeable evidence from morphological, behavioral, and electrophysiological studies encourages further investigation regarding the potential role of CCK-dependent synaptic plasticity in hippocampus dependent declarative memory.

Outbreak control management: Lessons from SARS-CoV-2 infections in 2020-2022 in Hong Kong, an international municipality with high-frequency travelers.

The control management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is one of the most challenges in the 21st century. By May 8th, 2022, SARS-CoV-2 has infected over 510 million people with 6.2 million death worldwide and over 1.2 million people with 9133 deaths in the fifth wave of infection in Hong Kong. The government responded rapidly in the early days of the 2020 outbreak, and the results were encouraging to control COVID-19 outbreak unavailable of vaccine. The quick responses to the epidemic alerts, for example, public education and control policies, kept residents safe from infection in the city with such a high population density and large-scale travelers. Nevertheless, the extremely high infectivity, Omicron variant infections, and the shortcomings of transmission control measures led to uncontrollable outbreak in 2022. The weak immunity groups, elderly and children, experienced a high hospitalization rate and mortality rate because of low vaccination rate. Currently, the infection is under well controlled. This study timely summarizes the challenges, policy, and lessons of SARS-CoV-2 outbreak control from 2020 to 2022. More importantly, the lesson and policy revealed from this study may be beneficial and applied to other cities with the outbreak of highly infectious SARS-CoV-2.

The fungivorous amoeba Protostelium aurantium targets redox homeostasis and cell wall integrity during intracellular killing of Candida parapsilosis.

Predatory interactions among microbes are major evolutionary driving forces for biodiversity. The fungivorous amoeba Protostelium aurantium has a wide fungal food spectrum including foremost pathogenic members of the genus Candida. Here we show that upon phagocytic ingestion by the amoeba, Candida parapsilosis is confronted with an oxidative burst and undergoes lysis within minutes of processing in acidified phagolysosomes. On the fungal side, a functional genomic approach identified copper and redox homeostasis as primary targets of amoeba predation, with the highly expressed copper exporter gene CRP1 and the peroxiredoxin gene PRX1 contributing to survival when encountered with P. aurantium. The fungicidal activity was largely retained in intracellular vesicles of the amoebae. Following their isolation, the content of these vesicles induced immediate killing and lysis of C. parapsilosis in vitro. Proteomic analysis identified 56 vesicular proteins from P. aurantium. Although completely unknown proteins were dominant, many of them could be categorised as hydrolytic enzymes targeting the fungal cell wall, indicating that fungal cell wall structures are under selection pressure by predatory phagocytes in natural environments. TAKE AWAY: The amoeba Protostelium aurantium feeds on fungi, such as Candida parapsilosis. Ingested yeast cells are exposed to reactive oxygen species. A copper exporter and a peroxiredoxin contribute to fungal defence. Yeast cells undergo intracellular lysis. Lysis occurs via a cocktail of hydrolytic enzymes from intracellular vesicles.

Interferon lambda 4 impacts the genetic diversity of hepatitis C virus.

Hepatitis C virus (HCV) is a highly variable pathogen that frequently establishes chronic infection. This genetic variability is affected by the adaptive immune response but the contribution of other host factors is unclear. Here, we examined the role played by interferon lambda-4 (IFN-λ4) on HCV diversity; IFN-λ4 plays a crucial role in spontaneous clearance or establishment of chronicity following acute infection. We performed viral genome-wide association studies using human and viral data from 485 patients of white ancestry infected with HCV genotype 3a. We demonstrate that combinations of host genetic variants, which determine IFN-λ4 protein production and activity, influence amino acid variation across the viral polyprotein - not restricted to specific viral proteins or HLA restricted epitopes - and modulate viral load. We also observed an association with viral di-nucleotide proportions. These results support a direct role for IFN-λ4 in exerting selective pressure across the viral genome, possibly by a novel mechanism.