A pharynx-to-brain axis controls pharyngeal inflammation-induced anxiety.

Anxiety is a remarkably common condition among patients with pharyngitis, but the relationship between these disorders has received little research attention, and the underlying neural mechanisms remain unknown. Here, we show that the densely innervated pharynx transmits signals induced by pharyngeal inflammation to glossopharyngeal and vagal sensory neurons of the nodose/jugular/petrosal (NJP) superganglia in mice. Specifically, the NJP superganglia project to norepinephrinergic neurons in the nucleus of the solitary tract (NTSNE). These NTSNE neurons project to the ventral bed nucleus of the stria terminalis (vBNST) that induces anxiety-like behaviors in a murine model of pharyngeal inflammation. Inhibiting this pharynx→NJP→NTSNE→vBNST circuit can alleviate anxiety-like behaviors associated with pharyngeal inflammation. This study thus defines a pharynx-to-brain axis that mechanistically links pharyngeal inflammation and emotional response.

Dynamic Contrast-enhanced MRI Quantification of Altered Vascular Permeability in Autoimmune Encephalitis.

Background Blood-brain barrier (BBB) permeability change is a possible pathologic mechanism of autoimmune encephalitis. Purpose To evaluate the change in BBB permeability in patients with autoimmune encephalitis as compared with healthy controls by using dynamic contrast-enhanced (DCE) MRI and to explore its predictive value for treatment response in patients. Materials and Methods This single-center retrospective study included consecutive patients with probable or possible autoimmune encephalitis and healthy controls who underwent DCE MRI between April 2020 and May 2021. Automatic volumetric segmentation was performed on three-dimensional T1-weighted images, and volume transfer constant (Ktrans) values were calculated at encephalitis-associated brain regions. Ktrans values were compared between the patients and controls, with adjustment for age and sex with use of a nonparametric approach. The Wilcoxon rank sum test was performed to compare Ktrans values of the good (improvement in modified Rankin Scale [mRS] score of at least two points or achievement of an mRS score of ≤2) and poor (improvement in mRS score of less than two points and achievement of an mRS score >2) treatment response groups among the patients. Results Thirty-eight patients with autoimmune encephalitis (median age, 38 years [IQR, 29-59 years]; 20 [53%] female) and 17 controls (median age, 71 years [IQR, 63-77 years]; 12 [71%] female) were included. All brain regions showed higher Ktrans values in patients as compared with controls (P < .001). The median difference in Ktrans between the patients and controls was largest in the right parahippocampal gyrus (25.1 × 10-4 min-1 [95% CI: 17.6, 43.4]). Among patients, the poor treatment response group had higher baseline Ktrans values in both cerebellar cortices (P = .03), the left cerebellar cortex (P = .02), right cerebellar cortex (P = .045), left cerebral cortex (P = .045), and left postcentral gyrus (P = .03) than the good treatment response group. Conclusion DCE MRI demonstrated that BBB permeability was increased in all brain regions in patients with autoimmune encephalitis as compared with controls, and baseline Ktrans values were higher in patients with poor treatment response in the cerebellar cortex, left cerebral cortex, and left postcentral gyrus as compared with the good response group. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Filippi and Rocca in this issue.

Regulation of headache response and transcriptomic network by the trigeminal ganglion clock.

OBJECTIVE: To characterize the circadian features of the trigeminal ganglion in a mouse model of headache. BACKGROUND: Several headache disorders, such as migraine and cluster headache, are known to exhibit distinct circadian rhythms of attacks. The circadian basis for these rhythmic pain responses, however, remains poorly understood. METHODS: We examined trigeminal ganglion ex vivo and single-cell cultures from Per2::LucSV reporter mice and performed immunohistochemistry. Circadian behavior and transcriptomics were investigated using a novel combination of trigeminovascular and circadian models: a nitroglycerin mouse headache model with mechanical thresholds measured every 6 h, and trigeminal ganglion RNA sequencing measured every 4 h for 24 h. Finally, we performed pharmacogenomic analysis of gene targets for migraine, cluster headache, and trigeminal neuralgia treatments as well as trigeminal ganglion neuropeptides; this information was cross-referenced with our cycling genes from RNA sequencing data to identify potential targets for chronotherapy. RESULTS: The trigeminal ganglion demonstrates strong circadian rhythms in both ex vivo and single-cell cultures, with core circadian proteins found in both neuronal and non-neuronal cells. Using our novel behavioral model, we showed that nitroglycerin-treated mice display circadian rhythms of pain sensitivity which were abolished in arrhythmic Per1/2 double knockout mice. Furthermore, RNA-sequencing analysis of the trigeminal ganglion revealed 466 genes that displayed circadian oscillations in the control group, including core clock genes and clock-regulated pain neurotransmitters. In the nitroglycerin group, we observed a profound circadian reprogramming of gene expression, as 331 of circadian genes in the control group lost rhythm and another 584 genes gained rhythm. Finally, pharmacogenetics analysis identified 10 genes in our trigeminal ganglion circadian transcriptome that encode target proteins of current medications used to treat migraine, cluster headache, or trigeminal neuralgia. CONCLUSION: Our study unveiled robust circadian rhythms in the trigeminal ganglion at the behavioral, transcriptomic, and pharmacogenetic levels. These results support a fundamental role of the clock in pain pathophysiology. PLAIN LANGUAGE SUMMARY: Several headache diseases, such as migraine and cluster headache, have headaches that occur at the same time each day. We learned that the trigeminal ganglion, an important pain structure in several headache diseases, has a 24-hour cycle that might be related to this daily cycle of headaches. Our genetic analysis suggests that some medications may be more effective in treating migraine and cluster headache when taken at specific times of the day.

Differences in factors associated with insomnia symptoms between patients with epilepsy with and without depressive symptoms.

OBJECTIVE: To determine if insomnia-related factors differ depending on the presence of depression in patients with epilepsy. METHODS: This cross-sectional multicenter study collected data on depressive symptoms, insomnia symptoms, and excessive daytime sleepiness, which were defined as a Patient Health Questionnaire-9 (PHQ-9) score of ≥ 10, an Insomnia Severity Index (ISI) score of ≥ 15, and an Epworth Sleepiness Scale (ESS) of ≥ 11, respectively. Further, uncontrolled seizures were defined as one or more seizures per month during antiseizure medications treatment. A stepwise logistic regression analysis was conducted, with a logistic regression with interaction terms performed to identify differences in insomnia-related factors depending on depressive symptoms. RESULTS: Of 282 adults with epilepsy (men, 58 %; mean age, 40.4 ± 13.9 years), a PHQ-9 score ≥ 10, an ISI score ≥ 15, an ESS score ≥ 11 were noted in 23.4 % (n = 66), 20.2 % (n = 57), and 12.8 % (n = 36), respectively. More patients with depressive symptoms had an ISI score ≥ 15 (56.1 % vs. 9.3 %; p < 0.001) than those without. In multiple logistic regression, uncontrolled seizures (odds ratio [OR], 4.896; p < 0.01), daytime sleepiness (OR, 5.369; p < 0.05), and a history of psychiatric disorders (OR, 3.971; p < 0.05) were identified as significant factors that were more likely to be associated with an ISI score ≥ 15; however, this was only true in patients without depressive symptoms. In contrast, use of perampanel (OR, 0.282; p < 0.05) was less likely associated, while female sex (OR, 3.178; p < 0.05) was more likely associated with an ISI score ≥ 15 only in patients with depressive symptoms. CONCLUSIONS: Insomnia-related factors in patients with epilepsy may differ between patients with and without depression. Our findings of different insomnia-related factors based on the presence of depression may facilitate the management of patients with epilepsy.

Chronic nicotine exposure elicits pain hypersensitivity through activation of dopaminergic projections to anterior cingulate cortex.

BACKGROUND: Cigarette smoking is commonly reported among chronic pain patients in the clinic. Although chronic nicotine exposure is directly linked to nociceptive hypersensitivity in rodents, underlying neurobiological mechanisms remain unknown. METHODS: Multi-tetrode recordings in freely moving mice were used to test the activity of dopaminergic projections from the ventral tegmental area (VTA) to pyramidal neurones in the anterior cingulate cortex (ACC) in chronic nicotine-treated mice. The VTA→ACC dopaminergic pathway was inhibited by optogenetic manipulation to detect chronic nicotine-induced allodynia (pain attributable to a stimulus that does not normally provoke pain) assessed by von Frey monofilaments (force units in g). RESULTS: Allodynia developed concurrently with chronic (28-day) nicotine exposure in mice (0.36 g [0.0141] vs 0.05 g [0.0018], P<0.0001). Chronic nicotine activated dopaminergic projections from the VTA to pyramidal neurones in the ACC, and optogenetic inhibition of VTA dopaminergic terminals in the ACC alleviated chronic nicotine-induced allodynia in mice (0.06 g [0.0064] vs 0.28 g [0.0428], P<0.0001). Moreover, optogenetic inhibition of Drd2 dopamine receptor signalling in the ACC attenuated nicotine-induced allodynia (0.07 g [0.0082] vs 0.27 g [0.0211], P<0.0001). CONCLUSIONS: These findings implicate a role of Drd2-mediated dopaminergic VTA→ACC pathway signalling in chronic nicotine-elicited allodynia.

Surgical Treatment for Sac Expansion Caused by Type II Endoleaks after Endovascular Aneurysm Repair of Abdominal Aortic Aneurysms/Iliac Aneurysms.

BACKGROUND: This study aimed to examine the outcomes of open surgery techniques involving sacotomy and suturing of the feeding vessels in patients with aneurysm sac expansion after endovascular aneurysm repair (EVAR). METHODS: Fourteen consecutive patients treated with sacotomy and suturing of feeding vessels for expanding aneurysm sacs with type II endoleaks following EVAR, between January 2018 and December 2022, were retrospectively included. All patients underwent preoperative digital subtraction angiography, and attempts were made to embolize the thick feeding vessels to reduce intraoperative bleeding. Age, sex, comorbidities, clinical presentation, aneurysm sac increase, morbidity, mortality, and follow-up were recorded. RESULTS: The median age of the patients was 72.89 ± 5.13 years old, and 13 (92.9%) patients were male. The sac size at the time of the open procedure was 107.89 ± 22.58 mm, and the extent of sac growth at the time of the open procedure was 37.50 ± 18.29 mm. The initial technical success rate of laparotomy and open ligation of the culprit arteries causing type II endoleaks was 92.9% (13/14). Among the patients, 5 (35.7%) had been treated with interventional embolization before the open procedure. One endograft was removed and replaced by a bifurcated Dacron graft because of distal dislocation in one patient. All patients recovered, and no deaths were recorded postoperatively. No patients had an eventful postoperative course or any subsequent graft-related complications during follow-up. CONCLUSIONS: Open surgical repair involving sacotomy and suturing of the feeding vessels appeared to have good outcomes in the treatment of patients with aneurysm sac expansion caused by type II endoleaks after EVAR. Preoperative embolization of feeding vessels can thus effectively reduce intraoperative bleeding.

Clinical Characteristics and Treatment Outcomes of Pulmonary Diseases Caused by Coinfections With Multiple Nontuberculous Mycobacterial Species.

BACKGROUND: Coinfections with multiple nontuberculous mycobacterial (NTM) species have not been widely studied. We aimed to evaluate the clinical characteristics and treatment outcomes in patients with NTM-pulmonary disease (PD) caused by coinfection with multiple NTM species. METHODS: We retrospectively reviewed patients with NTM-PD at a tertiary referral hospital in Korea between March 2012 and December 2018. Coinfection was defined as two or more species of NTM pathogens isolated from the same respiratory specimen or different specimens within three months. RESULTS: Among 1,009 patients with NTM-PD, 147 (14.6%) NTM coinfections were observed (average age 64.7 years, 69.4% women). NTM species were identified more frequently (median 6 vs. 3 times, P < 0.001) in the coinfection group than in the single species group, and follow-up duration was also longer in the coinfection group (median 44.9 vs. 27.1 months, P < 0.001). Mycobacterium avium complex (MAC) and M. abscessus and M. massiliense (MAB) were the dominant combinations (n = 71, 48.3%). For patients treated for over six months in the MAC plus MAB group (n = 31), sputum culture conversion and microbiological cure were achieved in 67.7% and 41.9% of patients, respectively. We divided the MAC plus MAB coinfection group into three subgroups according to the target mycobacteria; however, no statistical differences were found in the treatment outcomes. CONCLUSION: In NTM-PD cases, a significant number of multiple NTM species coinfections occurred. Proper identification of all cultured NTM species through follow-up is necessary to detect multispecies coinfections. Further research is needed to understand the nature of NTM-PD in such cases.

Risk Factors for Unfavorable Outcomes of Tuberculosis in Korea: Implications for Patient-Centered Care in Tuberculosis Treatment.

BACKGROUND: The treatment success rate for tuberculosis (TB) has stagnated at 80-81% in South Korea, indicating unsatisfactory outcomes. Enhancing treatment success rate necessitates the development of individualized treatment approaches for each patient. This study aimed to identify the risk factors associated with unfavorable treatment outcomes to facilitate tailored TB care. METHODS: We retrospectively analyzed the data of patients with active TB between January 2019 and December 2020 at a single tertiary referral center. We classified unfavorable treatment outcomes according to the 2021 World Health Organization guidelines as follows: "lost to follow-up" (LTFU), "not evaluated" (NE), "death," and "treatment failure" (TF). Moreover, we analyzed risk factors for each unfavorable outcome using Cox proportional hazard regression analysis. RESULTS: A total of 659 patients (median age 62 years; male 54.3%) were included in the study. The total unfavorable outcomes were 28.1%: 4.6% LTFU, 9.6% NE, 9.1% deaths, and 4.9% TF. Multivariate analysis showed that a culture-confirmed diagnosis of TB was associated with a lower risk of LTFU (adjusted hazard ratio [aHR], 0.25; 95% confidence interval [CI], 0.10-0.63), whereas the occurrence of adverse drug reactions (ADRs) significantly increased the risk of LTFU (aHR, 6.63; 95% CI, 2.63-16.69). Patients living far from the hospital (aHR, 4.47; 95% CI, 2.50-7.97) and those with chronic kidney disease (aHR, 3.21; 95% CI, 1.33-7.75) were at higher risk of being transferred out to other health institutions (NE). Higher mortality was associated with older age (aHR, 1.06; 95% CI, 1.04-1.09) and comorbidities. The ADRs that occurred during TB treatment were a risk factor for TF (aHR, 6.88; 95% CI, 2.24-21.13). CONCLUSION: Unfavorable outcomes of patients with TB were substantial at a tertiary referral center, and the risk factors for each unfavorable outcome varied. To improve treatment outcomes, close monitoring and the provision of tailored care for patients with TB are necessary.

Association between exposure to specific PM2.5 constituents and environment, lifestyle, and clinical parameters in patients with COPD.

This study investigated the correlation between the individual chemical constituents of particulate matter 2.5 µm (PM2.5) and respiratory parameters as well as the living environment and daily behaviors in patients with chronic obstructive pulmonary disease (COPD). Data were obtained from prospective COPD panel conducted in South Korea. Following collection via a microPEM, 18 metallic elements were determined using energy-dispersive X-ray fluorescence spectroscopy. All participants completed detailed questionnaires on living environments and lifestyle practices. Eighty-nine stable COPD patients (mean age 68.1 years; 94.4% male) were analyzed. Several constituents (titanium, aluminum, bromine, and silicone) were significantly associated with respiratory outcomes. Copper and manganese concentrations were significantly associated with the living environment. Increased ventilation time and air purifier operation were associated with lower concentrations of copper, silicone, barium, and titanium. These findings suggest varying relationships between PM2.5 constituents and clinical parameters in COPD patients, providing a basis for personalized interventions and future research.

Detection method for contact stress distribution of tapered roller bearings.

The axle box of high-speed train adopts double row tapered roller bearings as transmission parts, and the reliability of bearings directly affects the safety of train operation. Tapered roller bearings can withstand axial and radial loads, their service life being closely related to the distribution of contact stress. The test object is the axle box bearing of high-speed train. According to bearing's structural characteristics, based on the digital speckle correlation method (DSCM) and machine vision, the contact stress distribution detection devices for rollers and complete sets of bearings are developed respectively and an effective detection method is proposed. The contact stress data of the bearing which has reached the service life and the new bearing under the condition of no lubrication and grease lubrication are collected and normalized. Through the geometric relationship, based on the measured data of the selected detection points, the normal and tangential contact stress distribution of the roller and raceway under different contact conditions is obtained by data fitting. The test can be used as an evaluation basis for the effectiveness of bearing modification and provide reference for bearing design.

Complete mitochondrial genome of the southern painted turtle (Chrysemys dorsalis, Testudines: Emydidae) in Korea.

The complete mitochondrial genome of Chrysemys dorsalis in Korea was sequenced and characterized. The mitochondrial genome is 17,258 bp in length and the GC content is 39%. It is constituted of 37 genes, 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and a noncoding region. Phylogenetic analysis reveals that C. dorsalis forms a monophyletic group with C. picta turtles but is distinctly separated from them, aligning with previous findings. In Korea, C. dorsalis forms a discrete clade, separate from both native and invasive turtle species. No evidence of genetic disturbance or intermingling is observed. This is the first case of a complete mitochondrial genome from C. dorsalis and provides crucial data for understanding C. dorsalis and managing invasive species effectively, emphasizing the need for continued mitochondrial genome data accumulation.

Video-assisted thoracic surgery for an endobronchial ancient schwannoma obstructing the left main bronchus.

A schwannoma is a tumor that arises from the Schwann cells of the peripheral nerves. Primary pulmonary schwannomas are extremely rare, although they can occur anywhere in the body. Symptoms of endobronchial schwannoma vary depending upon the extent of bronchi blockage by the tumor. Schwannoma is a benign tumor. However, there is a risk of recurrence if a lesion that has developed extraluminal growth is incompletely resected. Here, a 76-year-old female patient presented with dyspnea and cough. An endobronchial tumor was identified originating from the left lower lobe bronchus and had collapsed the left lower lobe and grown to block most of the left main bronchus. Video-assisted thoracic surgery was performed to resect the left lower lobe. The tumor was diagnosed as an ancient schwannoma.

Improved organic and pesticide-free rice (Oryza sativa L.) authentication based on multiple stable isotope ratio analysis and rice milling state.

This study looked at the application of multiple bulk stable isotope ratio analysis to accurately authenticate organic rice and counteract organic fraud within the expanding global organic market. Variations of δ13C, δ15N, δ18O, and δ34S in organic, pesticide-free, and conventional rice were assessed across different milling states (brown, milled, and bran). Individual stable isotope ratio alone such as δ15N demonstrated limited capacity to correctly differentiate organic, pesticide-free, and conventional rice. A support vector machine model-incorporating δ13C, δ15N, δ18O, and δ34S in milled rice-yielded overall predictability (95%) in distinguishing organic, pesticide-free, and conventional rice, where δ18O emerged as the pivotal variable based on the feature weights in the SVM model. These findings suggest the potential of multi-isotope and advanced statistical approaches in combating organic fraud and ensuring authenticity in the food supply chain.

A Case Study: Electrically Assisted Stress Relief Annealing for Cold-Coiled Helical Automotive Springs.

This study experimentally investigated electrically assisted (EA) stress relief annealing for cold-coiled commercial automotive springs. In EA stress relief annealing, the temperature of a spring is rapidly increased to the annealing temperature (400 °C) and is held constant for a specified time using a pulsed electric current. Experimental findings show that the effectiveness of the EA stress relief annealing is superior to that of the conventional stress relief annealing, especially in terms of process time. The present study suggests that EA stress relief annealing, with properly selected process parameters, can effectively substitute for time-consuming conventional stress relief annealing using a furnace for cold-coiled automotive springs.

Molecular Identification of Spotted Fever Group Rickettsiae in Ticks in the Republic of Korea.

The Rickettsia species transmitted by ticks are mostly classified within the spotted fever group rickettsiae (SFGR), which causes tick-borne rickettsiosis. Although efforts have been made to investigate their prevalence in the Republic of Korea (ROK), research has been limited to certain areas. Furthermore, the pooling method for ticks does not fully reflect the exact infection rate. Therefore, we aimed to perform molecular identification of SFGR in ticks to elucidate the current prevalence of tick-borne rickettsiosis in the ROK. The SFGR of ticks was identified using polymerase chain reaction targeting the 17 kDa antigen, ompA, and gltA, followed by sequencing for species identification and phylogenetic analysis. In total, 302 ticks belonging to four species (Haemaphysalis flava, H. longicornis, Ixodes nipponensis, and Amblyomma testudinarium) were collected between April and November 2022. The overall SFGR infection rate was 26.8% (81/302 patients). Both adult and nymphal ticks and the SFGR infection rate increased during April-May, reaching their peaks in June, followed by a marked decline in August and July, respectively. Phylogenetic analysis revealed three species (R. monacensis, R. heilongjiangensis, and Candidatus R. jingxinensis) of SFGR. Thus, our results emphasize the importance of tick surveys for the prevention and management of tick-borne rickettsiosis.

Heat-Killed Lactococcus Lactis KC24 Ameliorates Scopolamine-Induced Memory Impairment in ICR Mice.

Heat-killed Lactococcus lactis KC24 (H-KC24) has been examined for its neuroprotective effects in SH-SY5Y cells. We hypothesized that H-KC24 could alleviate memory impairment through the gut-brain axis. Scopolamine (1 mg/kg/day) was administered to ICR mice to induce memory impairment. Low- and high-dose H-KC24 cells (1 × 109 and 2 × 109 CFU/day, respectively) or donepezil (DO, 2 mg/kg) were administered for 14 days. H-KC24 treatment alleviated the deleterious scopolamine-induced memory effects on the recognition index and object recognition ability in the novel object recognition test and the Y-maze test. Changes in neurotransmitters and synaptic plasticity were confirmed by measuring acetylcholine, acetylcholinesterase, choline acetyltransferase, brain-derived neurotrophic factor, cyclic AMP response element-binding protein, and phosphorylated cyclic AMP response element-binding protein expression in brain tissues. In the H-KC24 and DO groups, ß-secretase levels increased, whereas amyloid ß levels decreased, demonstrating that H-KC24 can improve memory impairment caused by oxidative stress. This study demonstrated the positive effects of H-KC24 in a scopolamine-induced memory impairment mouse model.

Multi-center Korean cohort study based on RNA-sequencing data targeting COPD patients.

In 2023, WHO ranked chronic obstructive pulmonary disease (COPD) as the third leading cause of death, with 3.23 million fatalities in 2019. The intricate nature of the disease, which is influenced by genetics, environment, and lifestyle, is evident. The effect of air pollution and changes in atmospheric substances because of global warming highlight the need for this research. These environmental shifts are associated with the emergence of various respiratory infections such as COVID-19. RNA sequencing is pivotal in airway diseases, including COPD, as it enables comprehensive transcriptome analysis, biomarker discovery, and uncovers novel pathways. It facilitates personalized medicine by tracking dynamic changes in gene expression in response to various triggers. However, the limited research on East Asian populations may overlook the unique nuances of COPD development and progression. Bridging this gap and using peripheral blood samples for systemic analysis are crucial for comprehensive and globally applicable COPD diagnosis and treatment.

Re-emergence of foot-and-mouth disease in the Republic of Korea caused by the O/ME-SA/Ind-2001e lineage.

The O/ME-SA/Ind-2001e foot-and-mouth disease virus (FMDV) lineage is a pandemic strain that has recently become dominant within East and Southeast Asia. During May 2023, this viral lineage spread to the Republic of Korea, where 11 outbreaks were detected on cattle and goat farms located in Cheongju and Jeungpyeong. Infected animals displayed typical FMD signs including vesicular lesions with drooling and anorexia. Molecular diagnostic testing and genetic analysis (VP1 sequencing) showed that the causative FMDVs belonged to the O/ME-SA/Ind-2001e lineage and shared the closest nucleotide identity (97.95-99.21%) to viruses that have been collected from Mongolia and South-East Asian countries. Phylogenetic analyses showed that these sequences were distinct to those collected from the previous Korean O/ME-SA/Ind-2001e lineage outbreaks in 2019, demonstrating that these cases are due to a new incursion of the virus into the country. Prompt implementation of emergency vaccination using antigenically matched serotype O vaccines (r1 value: 0.74-0.93), together with intensive active surveillance on farms surrounding the infected premises has successfully prevented further spread of FMD. These recent FMD outbreaks reinforce the importance of research to understand the risks associated with transboundary pathways in the region, in order to reduce the possibility of a further reintroduction of FMD into the Republic of Korea.

ARHGEF5 binds Drebrin and affects α-tubulin acetylation to direct neuronal morphogenesis and migration during mouse brain development.

Rho guanine nucleotide exchange factors (Rho GEFs) activate Rho GTPases, which act as molecular switches regulating various essential cellular functions. This study investigated the role of ARHGEF5, a Rho GEF known for its involvement in cell migration and invasion processes, in the context of brain development. We found that ARHGEF5 is essential for dendrite development during the early stages of neuronal growth. We also discovered that ARHGEF5 binds to Drebrin E, which is vital for coordinating actin and microtubule dynamics, and facilitates the interaction between Drebrin E and Cyclin-dependent kinase 5, which phosphorylates Drebrin E. Notably, ARHGEF5 deficiency resulted in a decrease in acetylated α-tubulin levels, and the expression of an α-tubulin acetylation mimetic mutant (K40Q) rescued the defects in dendrite development and neuronal migration, suggesting ARHGEF5's role in modulating microtubule stability. Additionally, ARHGEF5 was shown to influence Golgi positioning in the leading processes of migrating cortical neurons during brain development. Our study suggests that ARHGEF5 plays a crucial role in integrating cytoskeletal dynamics with neuronal morphogenesis and migration processes during brain development.

Molecular Analysis of Tick-Borne Bacterial Pathogens from Ticks Infesting Animal Hosts in Kyrgyzstan, 2021.

This study investigated the prevalence of Anaplasma and Ehrlichia in 494 engorged ticks collected from various animal hosts, including cattle, horses, sheep, chickens, dogs, and cats, in six regions of northern Kyrgyzstan. Ten tick species, belonging to two families and six genera, were identified based on CO1, 16S rRNA, and ITS2 genes: Argas persicus (26.5%), Haemaphysalis punctata (18.0%), Dermacentor spp. (16.0%), Rhipicephalus annulatus (11.8%), R. turanicus (10.9%), D. marginatus (7.7%), Hyalomma scupense (4.5%), Hy. marginatum (3.8%), R. sangineus complex (0.6%), and Ornithodoros lahorensis (0.2%). PCR analysis revealed a 15.0% (74/494) overall infection rate of Anaplasma and Ehrlichia. Anaplasma species were found in six tick species and were identified as A. bovis (n = 44), Anaplasma spp. (n = 20), A. ovis (n = 5), and A. capra (n = 2). Ehrlichia species were found only in H. punctata (n = 5) and identified as E. chaffeensis (n = 1) and Ehrlichia spp. (n = 4). Additionally, two H. punctata were co-infected with Anaplasma and Ehrlichia. This is the first study to investigate tick-borne bacterial pathogens in ticks collected from animal hosts in Kyrgyzstan. Our findings contribute to a better understanding of the epidemiology and emergence of tick-borne infections in Kyrgyzstan.