Prickle2 and Igsf9b Coordinately Regulate the Cytoarchitecture of the Axon Initial Segment.

Prickle2 has been identified in genetic studies of subjects with autism spectrum disorder (ASD) and epilepsy, but the pathological mechanism of Prickle2 remains to be fully understood. Proteomic analysis of Prickle2 with mass spectrometry revealed twenty-eight Prickle2 interactors, including immunoglobulin superfamily member 9b (Igsf9b), in the brain. Here, because Igsf9 family proteins are associated with psychiatric diseases and seizures, we studied the physiological interaction between Prickle2 and Igsf9b. Prickle2 colocalized with Igsf9b in cultured hippocampal neurons. Knockdown of Prickle2 affected the subcellular localization of Igsf9b. Interestingly, Igsf9b localized along axonal processes in a pattern opposite to the ASD-related molecule ANK3/AnkG. AnkG is a major component of the axon initial segment (AIS), where a variety of ASD and epilepsy susceptibility proteins accumulate. Igsf9b-knockdown neurons displayed altered AnkG localization. Prickle2 depletion caused defects in AnkG and voltage-gated Na+ channel localization, resulting in altered network activity. These results support the idea that Prickle2 regulates AnkG distribution by controlling the proper localization of Igsf9b. The novel function of Prickle2 in AIS cytoarchitecture provides new insights into the shared pathology of ASD and epilepsy.Key words: Prickle2, Igsf9b, axon initial segment, neuronal excitability, ASD.

Prevalence of Antibiotic-Resistant Shigella spp. in Bangladesh: A Systematic Review and Meta-Analysis of 44,519 Samples.

Shigella is the leading global etiological agent of shigellosis, especially in poor and underdeveloped or developing nations with insufficient sanitation such as Bangladesh. Antibiotics are the only treatment option for the shigellosis caused by Shigella spp. as no effective vaccine exists. However, the emergence of antimicrobial resistance (AMR) poses a serious global public health concern. Therefore, a systematic review and meta-analysis were conducted to establish the overall drug resistance pattern against Shigella spp. in Bangladesh. The databases of PubMed, Web of Science, Scopus, and Google Scholar were searched for relevant studies. This investigation comprised 28 studies with 44,519 samples. Forest and funnel plots showed any-drug, mono-drug, and multi-drug resistance. Any fluoroquinolone had a resistance rate of 61.9% (95% CI: 45.7-83.8%), any trimethoprim-sulfamethoxazole-60.8% (95% CI: 52.4-70.5%), any azithromycin-38.8% (95% CI: 19.6-76.9%), any nalidixic acid-36.2% (95% CI: 14.2-92.4%), any ampicillin-34.5% (95% CI: 25.0-47.8%), and any ciprofloxacin-31.1% (95% CI: 11.9-81.3%). Multi-drug-resistant Shigella spp. exhibited a prevalence of 33.4% (95% CI: 17.3-64.5%), compared to 2.6% to 3.8% for mono-drug-resistant strains. Since resistance to commonly used antibiotics and multidrug resistance were higher, a judicious use of antibiotics, the promotion of infection control measures, and the implementation of antimicrobial surveillance and monitoring programs are required to tackle the therapeutic challenges of shigellosis.