Tracing Strategies Research Articles

Thalamocortical Circuit Controls Neuropathic Pain via Up-regulation of HCN2 in the Ventral Posterolateral Thalamus

The thalamocortical (TC) circuit is closely associated with pain processing. The hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 channel is predominantly expressed in the ventral posterolateral thalamus (VPL) that has been shown to mediate neuropathic pain. However, the role of VPL HCN2 in modulating TC circuit activity is largely unknown. Here, by using optogenetics, neuronal tracing, electrophysiological recordings, and virus knockdown strategies, we showed that the activation of VPL TC neurons potentiates excitatory synaptic transmission to the hindlimb region of the primary somatosensory cortex (S1HL) as well as mechanical hypersensitivity following spared nerve injury (SNI)-induced neuropathic pain in mice. Either pharmacological blockade or virus knockdown of HCN2 (shRNA-Hcn2) in the VPL was sufficient to alleviate SNI-induced hyperalgesia. Moreover, shRNA-Hcn2 decreased the excitability of TC neurons and synaptic transmission of the VPL–S1HL circuit. Together, our studies provide a novel mechanism by which HCN2 enhances the excitability of the TC circuit to facilitate neuropathic pain.

Single-cell RNA sequencing and lineage tracing confirm mesenchyme to epithelial transformation (MET) contributes to repair of the endometrium at menstruation.

The human endometrium experiences repetitive cycles of tissue wounding characterised by piecemeal shedding of the surface epithelium and rapid restoration of tissue homeostasis. In this study, we used a mouse model of endometrial repair and three transgenic lines of mice to investigate whether epithelial cells that become incorporated into the newly formed luminal epithelium have their origins in one or more of the mesenchymal cell types present in the stromal compartment of the endometrium. Using scRNAseq, we identified a novel population of PDGFRb + mesenchymal stromal cells that developed a unique transcriptomic signature in response to endometrial breakdown/repair. These cells expressed genes usually considered specific to epithelial cells and in silico trajectory analysis suggested they were stromal fibroblasts in transition to becoming epithelial cells. To confirm our hypothesis we used a lineage tracing strategy to compare the fate of stromal fibroblasts (PDGFRa+) and stromal perivascular cells (NG2/CSPG4+). We demonstrated that stromal fibroblasts can undergo a mesenchyme to epithelial transformation and become incorporated into the re-epithelialised luminal surface of the repaired tissue. This study is the first to discover a novel population of wound-responsive, plastic endometrial stromal fibroblasts that contribute to the rapid restoration of an intact luminal epithelium during endometrial repair. These findings form a platform for comparisons both to endometrial pathologies which involve a fibrotic response (Asherman's syndrome, endometriosis) as well as other mucosal tissues which have a variable response to wounding.

1881. Detection of SARS-CoV-2 Transmission on a College Campus using a Combined Contact Tracing and Molecular Strategy

Abstract Background SARS-CoV-2 has caused unprecedented global disruption following its introduction into the human population. Beginning in August 2021, a residential college initiated an asymptomatic testing protocol using PCR-based detection of human saliva samples (Thermofisher, TaqPath SARS-CoV-2 Assay; QuantStudio v1.3). In January 2021 all students were invited to campus and were required to test once or twice weekly in an effort to isolate those positive (cases) as early as possible and minimize transmission. Methods Cases were contacted within 12 hours by trained clinical staff and interviewed with a standardized questionnaire to determine contacts and exposures. Positive samples were submitted for RNA-Seq analysis (ARTIC amplicon sequencing protocol, Illumina MiSeq) and analyzed using Nextclade and USHER (comparison data from GISAID). Using this sequence data, we monitored the evolution, transmission, and emergence of variants over time in the campus community. Results In March 2022 a one-week break and the activities preceding it were followed by an outbreak of COVID among campus members. All cases were attributed to the Omicron variant. Based on traditional contact tracing 10 presumed clusters of transmission were identified (34 students). Sequence data from these 34 samples were assembled to identify phylogenetic and molecular patterns of similarity. Several molecular signatures were identified. In a group of 5 cases, all were Omicron BA.2.9; these individuals comprised a clinical cluster of students who had travelled together. Other lineages were BA.2 (N=26), BA.1(N=2), BA.2.12. (N=3), BA.2.3 (N=1) and an Omicron Clade 21M variant that appeared to be a BA.1/BA.2 recombinant (N=2). The BA.2.12 samples were contributed over 2 days; they were found in two different clusters (a social club and an artistic group), demonstrating likely transmission between members. The BA.2 samples were distributed across a wide number of student groups, and while not identical with one another, did not fall into the clusters identified by contact tracing, suggesting endemic transmission across our campus. Conclusion This analysis demonstrates that molecular analysis of SARS-CoV-2 transmission can supplement and inform the data provided by clinical/epidemiological analysis of cases. Disclosures All Authors: No reported disclosures.

The Effect of Lymphangiogenesis in Transplant Arteriosclerosis.

Transplant arteriosclerosis is a major complication in long-term survivors of heart transplantation. Increased lymph flow from donor heart to host lymph nodes has been reported to play a role in transplant arteriosclerosis, but how lymphangiogenesis affects this process is unknown. Vascular allografts were transplanted among various combinations of mice, including wild-type, Lyve1-CreERT2;R26-tdTomato, CAG-Cre-tdTomato, severe combined immune deficiency, Ccr2KO, Foxn1KO, and lghm/lghdKO mice. Whole-mount staining and 3-dimensional reconstruction identified lymphatic vessels within the grafted arteries. Lineage tracing strategies delineated the cellular origin of lymphatic endothelial cells. Adeno-associated viral vectors and a selective inhibitor were used to regulate lymphangiogenesis. Lymphangiogenesis within allograft vessels began at the anastomotic sites and extended from preexisting lymphatic vessels in the host. Tertiary lymphatic organs were identified in transplanted arteries at the anastomotic site and lymphatic vessels expressing CCL21 (chemokine [C-C motif] ligand 21) were associated with these immune structures. Fibroblasts in the vascular allografts released VEGF-C (vascular endothelial growth factor C), which stimulated lymphangiogenesis into the grafts. Inhibition of VEGF-C signaling inhibited lymphangiogenesis, neointima formation, and adventitial fibrosis of vascular allografts. These studies identified VEGF-C released from fibroblasts as a signal stimulating lymphangiogenesis extending from the host into the vascular allografts. Formation of lymphatic vessels plays a key role in the immune response to vascular transplantation. The inhibition of lymphangiogenesis may be a novel approach to prevent transplant arteriosclerosis.

COVID-19 impact on index testing services and programmatic cost in 5 high HIV prevalence Indian districts

BackgroundRestrictions to curb the first wave of COVID-19 in India resulted in a decline in facility-based HIV testing rates, likely contributing to increased HIV transmission and disease progression. The programmatic and economic impact of COVID-19 on index testing, a standardized contact tracing strategy, remains unknown.MethodsRetrospective programmatic and costing data were analyzed under a US government-supported program to assess the pandemic’s impact on the programmatic outcomes and cost of index testing implemented in two Indian states (Maharashtra and Andhra Pradesh). We compared index testing continuum outcomes during lockdown (April–June 2020) and post-lockdown (July–Sept 2020) relative to pre-lockdown (January–March 2020) by estimating adjusted rate ratios (aRRs) using negative binomial regression. Startup and recurrent programmatic costs were estimated across geographies using a micro-costing approach. Per unit costs were calculated for each index testing continuum outcome.ResultsPre-lockdown, 2431 index clients were offered services, 3858 contacts were elicited, 3191 contacts completed HIV testing, 858 contacts tested positive, and 695 contacts initiated ART. Compared to pre-lockdown, the number of contacts elicited decreased during lockdown (aRR = 0.13; 95% CI: 0.11–0.16) and post-lockdown (aRR = 0.49; 95% CI: 0.43–0.56); and the total contacts newly diagnosed with HIV also decreased during lockdown (aRR = 0.22; 95% CI: 0.18–0.26) and post-lockdown (aRR = 0.52; 95% CI: 0.45–0.59). HIV positivity increased from 27% pre-lockdown to 40% during lockdown and decreased to 26% post-lockdown. Further, ART initiation improved from 81% pre-lockdown to 88% during lockdown and post-lockdown. The overall cost to operate index testing was $193,457 pre-lockdown and decreased during lockdown to $132,177 (32%) and $126,155 (35%) post-lockdown. Post-lockdown unit cost of case identification rose in facility sites ($372) compared to pre-lockdown ($205), however it decreased in community-based sites from pre-lockdown ($277) to post-lockdown ($166).ConclusionsThere was a dramatic decline in the number of index testing clients in the wake of COVID-19 restrictions that resulted in higher unit costs to deliver services; yet, improved linkage to ART suggests that decongesting centres could improve efficiency. Training index testing staff to provide support across services including non-facility-based HIV testing mechanisms (i.e., telemedicine, HIV self-testing, community-based approaches) may help optimize resources during public health emergencies.

Risk factors for SARS-CoV-2 transmission in close contacts of adults at high risk of infection due to occupation: results from the contact tracing strategy of the CoVIDA epidemiological surveillance study in Bogotá, Colombia, in 2020–2021

ObjectivesTo estimate the risk factors for SARS-CoV-2 transmission in close contacts of adults at high risk of infection due to occupation, participants of the CoVIDA study, in Bogotá D.C., Colombia.SettingThe...

Modelling the impact of school reopening and contact tracing strategies on Covid-19 dynamics in different epidemiologic settings in Brazil.

We simulate the impact of school reopening during the COVID-19 pandemic in three major urban centers in Brazil to identify the epidemiological indicators and the best timing for the return of in-school activities and the effect of contact tracing as a mitigation measure. Our goal is to offer guidelines for evidence-based policymaking. We implement an extended SEIR model stratified by age and considering contact networks in different settings - school, home, work, and community, in which the infection transmission rate is affected by various intervention measures. After fitting epidemiological and demographic data, we simulate scenarios with increasing school transmission due to school reopening, and also estimate the number of hospitalization and deaths averted by the implementation of contact tracing. Reopening schools results in a non-linear increase in reported COVID-19 cases and deaths, which is highly dependent on infection and disease incidence at the time of reopening. When contact tracing and quarantining are restricted to school and home settings, a large number of daily tests is required to produce significant effects in reducing the total number of hospitalizations and deaths. Policymakers should carefully consider the epidemiological context and timing regarding the implementation of school closure and return of in-person school activities. While contact tracing strategies prevent new infections within school environments, they alone are not sufficient to avoid significant impacts on community transmission.

Run-Length-Based River Skeleton Line Extraction from High-Resolution Remote Sensed Image

Automatic extraction of the skeleton lines of river systems from high-resolution remote-sensing images has great significance for surveying and managing water resources. A large number of existing methods for the automatic extraction of skeleton lines from raster images are primarily used for simple graphs and images (e.g., fingerprint, text, and character recognition). These methods generally are memory intensive and have low computational efficiency. These shortcomings preclude their direct use in the extraction of skeleton lines from large volumes of high-resolution remote-sensing images. In this study, we developed a method to extract river skeleton lines based entirely on run-length encoding. This method attempts to replace direct raster encoding with run-length encoding for storing river data, which can considerably compress raster data. A run-length boundary tracing strategy is used instead of complete raster matrix traversal to quickly determine redundant pixels, thereby significantly improving the computational efficiency. An experiment was performed using a 0.5 m-resolution remote-sensing image of Yiwu city in the Chinese province of Zhejiang. Raster data for the rivers in Yiwu were obtained using both the DeepLabv3+ deep learning model and the conventional visual interpretation method. Subsequently, the proposed method was used to extract the skeleton lines of the rivers in Yiwu. To compare the proposed method with the classical raster-based skeleton line extraction algorithm developed by Zhang and Suen in terms of memory consumption and computational efficiency, the visually interpreted river data were used to generate skeleton lines at different raster resolutions. The results showed that the proposed method consumed less than 1% of the memory consumed by the classical method and was over 10 times more computationally efficient. This finding suggests that the proposed method has the potential for river skeleton line extraction from terabyte-scale remote-sensing image data on personal computers.

Resistance patterns among drug-resistant tuberculosis patients and trends-over-time analysis of national surveillance data in Gabon, Central Africa

ObjectiveRoutinely generated surveillance data are important for monitoring the effectiveness of MDR-TB control strategies. Incidence of rifampicin-resistant tuberculosis (RR-TB) is a key indicator for monitoring MDR-TB.MethodsIn a longitudinal nationwide retrospective study, 8 years (2014–2021) of sputum samples from presumptively drug-resistant tuberculosis patients from all regions of Gabon were referred to the national tuberculosis reference laboratory. Samples were analysed using GeneXpert MTB/RIF and Genotype MTBDRsl version 2/Line Probe Assay.ResultsOf 3057 sputum samples from presumptive tuberculosis patients, both from local hospital and from referral patients, 334 were RR-TB. The median patient age was 33 years (interquartile range 26–43); one third was newly diagnosed drug-resistant tuberculosis patients; one-third was HIV-positive. The proportion of men with RR-TB was significantly higher than that of women (55% vs 45%; p < 0.0001). Patients aged 25–35 years were most affected (32%; 108/334). The cumulative incidence of RR-TB was 17 (95% CI 15–19)/100,000 population over 8 years. The highest incidences were observed in 2020 and 2021. A total of 281 samples were analysed for second-line drug resistance. The proportions of study participants with MDR-TB, pre-XDR-TB and XDR-TB were 90.7% (255/281), 9% (25/281) and 0.3% (1/281), respectively. The most-common mutations in fluoroquinolones resistance isolates was gyrA double mutation gyrA MUT3B and MUT3C (23%; 4/17). Most (64%; 6/8) second-line injectable drugs resistance isolates were characterised by missing both rrs WT2 and MUT2 banding.ConclusionThe increasing incidence of MDR-TB infection in Gabon is alarming. It is highest in the 25–35 years age category. The incidence of MDR-TB infection in treatment-naïve patients calls for case finding and contact tracing strategy improvement.

Learning from COVID-19: The inclusion of vulnerable groups in COVID-19 responses across Europe

Abstract Background More than two years into the pandemic, many European countries have begun to evaluate their COVID-19 public health responses and draw lessons for future preparedness. As the COVID-19 crisis has exacerbated intersectional social and health inequalities, it is pertinent to evaluate the extent to which COVID-19 responses have successfully responded to the diverse needs of various vulnerable groups. We present a comparative analysis of how evaluations of European COVID-19 responses have assessed efforts to adapt or tailor COVID-19 responses to vulnerable groups, focusing on public testing and tracing strategies and vaccination campaigns. Methods We draw on data collected in the H2020 project COVINFORM. We combine insights from qualitative interviews conducted with public health policy- and decision makers in COVINFORM partner countries with a document review of available evaluations of COVID-19 responses published by both government and academic actors between March 2020 and June 2022. Results Across countries, evaluations of COVID-19 responses show that efforts to adapt or target public health responses to specific vulnerable groups became more common as the pandemic stretched on. Differences across countries were observed in relation to which groups were considered particularly vulnerable; the types of responses considered successful; as well as the organisational/governmental level at which responses were coordinated. Analyses reveal that the heavy emphasis on medical vulnerability distracted from efforts to address broader, structural inequalities, complicating the development of tailor-made policies. Conclusions The results inform ongoing policies that deal with the long-term consequences of the COVID-19 pandemic and aim to reduce disproportionate impacts faced by vulnerable groups. Our findings also add to a better understanding of how future preparedness structures should take into account how pandemic measures have unequal impacts. Key messages • As the COVID-19 crisis has exacerbated intersectional social and health inequalities, it is important to learn from efforts to adapt or tailor COVID-19 responses to vulnerable groups. • The findings demonstrate how across Europe, the combination of particular sets of country-specific COVID-19 responses, tailor-made or not, yield specific consequences for vulnerable groups.

Cell Fate of Retinal Progenitor Cells: In Ovo UbC-StarTrack Analysis.

Clonal cell analysis outlines the ontogenic potential of single progenitor cells, allowing the elucidation of the neural heterogeneity among different cell types and their lineages. In this work, we analyze the potency of retinal stem/progenitor cells through development using the chick embryo as a model. We implemented in ovo the clonal genetic tracing strategy UbC-StarTrack for tracking retinal cell lineages derived from individual progenitors of the ciliary margin at E3.5 (HH21-22). The clonal assignment of the derived-cell progeny was performed in the neural retina at E11.5-12 (HH38) through the identification of sibling cells as cells expressing the same combination of fluorophores. Moreover, cell types were assessed based on their cellular morphology and laminar location. Ciliary margin derived-cell progenies are organized in columnar associations distributed along the peripheral retina with a limited tangential dispersion. The analysis revealed that, at the early stages of development, this region harbors multipotent and committed progenitor cells.

Contact Tracing Strategies for COVID-19 Prevention and Containment: A Scoping Review

Coronavirus Disease 2019 (COVID-19) spreads rapidly and is easily contracted by individuals who come near infected persons. With this nature and rapid spread of the contagion, different types of research have been conducted to investigate how non-pharmaceutical interventions can be employed to contain and prevent COVID-19. In this review, we analyzed the key elements of digital contact tracing strategies developed for the prevention and containment of the dreaded epidemic since its outbreak. We carried out a scoping review through relevant studies indexed in three databases, namely Google Scholar, PubMed, and ACM Digital Library. Using some carefully defined search terms, a total of 768 articles were identified. The review shows that 86.32% (n = 101) of the works focusing on contact tracing were published in 2020, suggesting there was an increased awareness that year, increased research efforts, and the fact that the pandemic was given a very high priority by most journals. We observed that many (47.86%, n = 56) of the studies were focused on design and implementation issues in the development of COVID-19 contact tracing systems. In addition, has been established that most of the studies were conducted in 41 countries and that contract tracing app development are characterized by some sensitive issues, including privacy-preserving and case-based referral characteristics.

Murine foetal liver supports limited detectable expansion of life-long haematopoietic progenitors.

Current dogma asserts that the foetal liver (FL) is an expansion niche for recently specified haematopoietic stem cells (HSCs) during ontogeny. Indeed, between embryonic day of development (E)12.5 and E14.5, the number of transplantable HSCs in the murine FL expands from 50 to about 1,000. Here we used a non-invasive, multi-colour lineage tracing strategy to interrogate the embryonic expansion of murine haematopoietic progenitors destined to contribute to the adult HSC pool. Our data show that this pool of fated progenitors expands only two-fold during FL ontogeny. Although Histone2B-GFP retention in vivo experiments confirmed substantial proliferation of phenotypic FL-HSC between E12.5 and E14.5, paired-daughter cell assays revealed that many mid-gestation phenotypic FL-HSCs are biased to differentiate, rather than self-renew, relative to phenotypic neonatal and adult bone marrow HSCs. In total, these data support a model in which the FL-HSC pool fated to contribute to adult blood expands only modestly during ontogeny.

Lessons learnt of the COVID-19 contact tracing strategy in Islamabad Capital Territory, Pakistan using systems thinking processes.

The strategy of test, trace and isolate has been promoted and seen as a crucial tool in the fight against the COVID-19 pandemic. As simple as the slogan sounds, effectively implementing it turns into a complex endeavor with multiple moving parts and the need for multisector collaboration. In this study, we apply a systems thinking lens to analyse the design and implementation of the contact tracing strategy for COVID-19 in the district of Islamabad, Pakistan. The data collection included participatory observation, reflective exercises, key informant interviews and participatory workshops with district health managers and health providers. The information gathered was structured using process and stakeholder mapping to identify the lessons learned of the COVID-19 contact tracing strategy. The results showed that the elements crucial for implementation were, good coordination during a crisis, available resources mobilized effectively and establishment of early active surveillance for contact tracing. Furthermore, the main aspects to be improved were lack of preparedness and existing surveillance systems and task shifting leading to impact on regular health services. The results of this study highlight the importance of developing information systems that are coherent with existing processes and resources, even in times of crisis.

The acceptability of testing contacts of confirmed COVID-19 cases using serial, self-administered lateral flow devices as an alternative to self-isolation.

Introduction. Evidence suggests that although people modify their behaviours, full adherence to self-isolation guidance in England may be suboptimal, which may have a detrimental impact on COVID-19 transmission rates.Hypothesis. Testing asymptomatic contacts of confirmed COVID-19 cases for the presence of SARS-CoV-2 could reduce onward transmission by improving case ascertainment and lessen the impact of self-isolation on un-infected individuals.Aim. This study investigated the feasibility and acceptability of implementing a 'test to enable approach' as part of England's tracing strategy.Methodology. Contacts of confirmed COVID-19 cases were offered serial testing as an alternative to self-isolation using daily self-performed lateral flow device (LFD) tests for the first 7 days post-exposure. Asymptomatic participants with a negative LFD result were given 24 h of freedom from self-isolation between each test. A self-collected confirmatory PCR test was performed on testing positive or at the end of the LFD testing period.Results. Of 1760 contacts, 882 consented to daily testing, of whom 812 individuals were within 48 h of exposure and were sent LFD testing packs. Of those who declined to participate, 39.1% stated they had already accessed PCR testing. Of the 812 who were sent LFD packs, 570 (70.2%) reported one or more LFD results; 102 (17.9%) tested positive. Concordance between reported LFD result and a supplied LFD image was 97.1%. In total, 82.8% of PCR-positive samples and 99.6% of PCR-negative samples were correctly detected by LFD. The proportion of secondary cases from contacts of those who participated in the study and tested positive (6.3%; 95% CI: 3.4-11.1%) was comparable to a comparator group who self-isolated (7.6%; 95% CI: 7.3-7.8%).Conclusion. This study shows a high acceptability, compliance and positivity rates when using self-administered LFDs among contacts of confirmed COVID-19 cases. Offering routine testing as a structured part of the contact tracing process is likely to be an effective method of case ascertainment.

Comparison of COVID-19 contact-tracing apps in the context of public policy: the cases of Turkey and South Korea

The healthcare systems of almost every country have been facing an unprecedented crisis since the beginning of the COVID-19 pandemic in March 2020. In response, numerous countries have designed and launched their unique applications to inform their citizens about COVID-19 and to follow their health situation. While South Korea has been showing an effective fight against COVID-19, Turkey is one of the most affected ones by the virus. This paper aims to identify key differences and similarities between the contact tracing apps that are used by Turkey and South Korea during COVID-19. In this way, it addresses how two members of the Organization for Economic Co-operation and Development (OECD), one developing (Turkey) and other developed (South Korea) countries, integrated their public policies and crisis management responses with the mobile phone applications and at what scale they are successful. Also, this paper investigates how these differences/similarities between their applications have affected their paths in the pandemic. Comparing their applications, it discusses policy-making processes, technological differences, and contact tracing strategies with policy recommendations for other countries.

Evaluation of indocyanine green combined with methylene blue staining in sentinel lymph node biopsy of breast cancer.

BackgroundMethylene blue as tracer used in sentinel lymph node biopsy (SLNB) have low detection rate and high false negative rate. Indocyanine green (ICG) can detect the flow of subcutaneous lymphatic vessels and the position of lymph nodes dynamically. This study sought to evaluate the efficacy of ICG combined with methylene blue staining in SLNB of breast cancer.MethodsOne hundred and fifty-six early breast cancer patients treated at our hospital from July 2020 to May 2022 were enrolled in this study. SLNB was performed by ICG combined with methylene blue staining under the guidance of the fluorescent tracer navigation system FLI-10B. Standard axillary lymph node dissection (ALND) was performed in patients with sentinel lymph node (SLN) metastasis confirmed by intraoperative frozen pathology, while low ALND was performed in patients with negative SLNs. According to the staining condition, the SLNs were divided into: (I) the combined group (SLNs with methylene blue staining and/or ICG luminescence); (II) the methylene blue group (SLNs with methylene blue staining alone); and (III) the ICG group (SLNs with ICG luminescence alone). The detection rate, accuracy, sensitivity, and false negative rate of SLNB were compared among the 3 groups.ResultsA total of 592 SLNs were detected in the combined group (average 3.8 SLNs), yielding a detection rate of 97.4%; the accuracy, sensitivity, and false negative rates were 97.4%, 92.7%, and 7.3%. In the methylene blue group, 390 SLNs were detected (average 2.5 SLNs), yielding a detection rate of 84.6%; the accuracy, sensitivity, and false negative rates were 83.3%, 89.1%, and 10.9%. A total of 483 SLNs were detected in the ICG group (average 3.1 SLNs), the detection rate was 92.9%; the accuracy, sensitivity and false negative rates were 91.7%, 90.9%, and 9.1%. The average number of detected SLNs, detection rate and accuracy rate in the combined group were higher than those in the methylene blue group (P<0.05), and the accuracy rate of the combined group was higher than that of the ICG group (P<0.05).ConclusionsICG combined with methylene blue staining is a promising and effective tracing strategy in the SLNB of breast cancer with high detection and accuracy rates.

Connectivity and functional characterization of the mouse contralateral projecting neurons in basolateral amygdala

Amygdala is widely known as a critical neural hub for modulating negative emotions such as fear and anxiety. Recent studies have shown that the basolateral amygdala (BLA) has reciprocal innervation, which plays an important role in regulating social interaction and associative memory. However, the connectivity pattern and functional role of the contralateral projecting BLA neurons in stress-related anxiety are not fully understood. Here, using the virus tracing strategy, we first characterized the connectivity pattern of the contralateral projecting neurons in BLA. Then, we examined the effect of stress on the functional changes of those specific neuronal populations using a mouse model of inescapable footshock stress. The results showed that the fibers of the contralateral projecting BLA neurons labeled by enhanced green fluorescent protein (EGFP) have no collateral projections to the ipsilateral or contralateral hippocampus. Interestingly, they have some collateral projections to the ipsilateral medial prefrontal cortex. Behavioral results showed that footshock stress increases the anxiety-like behavior in mice; however, the excitatory synaptic transmission and intrinsic excitability of the contralateral projecting BLA neurons measured by whole-cell patch clamp recording did not change after stress exposure. In conclusion, our results indicate that contralateral projecting BLA neurons may not contribute to footshock stress-related anxiety-like behavior.

Cobalt Ferrite Magnetic Nanoparticles for Tracing Mesenchymal Stem Cells in Tissue: A Preliminary Study

Therapy with mesenchymal stem cells (MSCs) is promising in many diseases. Evaluation of their efficacy depends on adequate follow-up of MSCs after transplantation. Several studies have shown that MSCs can be labeled and subsequently visualized with magnetic nanoparticles (NPs). We investigated the homing of MSCs labeled with magnetic cobalt ferrite NPs in experimentally induced acute kidney injury in mice. To explore the homing of MSCs after systemic infusion into mice, we developed a pre-infusion strategy for optimal tracing and identification of MSCs with polyacrylic acid-coated cobalt ferrite (CoFe2O4) NPs by light and transmission electron microscopy (TEM) in various organs of mice with cisplatin-induced acute kidney injury and control mice. By correlative microscopy, we detected MSCs labeled with NPs in the lungs, spleen, kidney, and intestine of cisplatin-treated mice and in the lungs and spleen of control mice. Our results confirm that labeling MSCs with metal NPs did not affect the ultrastructure of MSCs and their ability to settle in various organs. This study demonstrates the usefulness of cobalt ferrite NPs in ex vivo visualization of MSCs and offers correlative microscopy as a useful method in routine histopathology laboratories for tracing MSCs in paraffin-embedded tissue.

Investigation on Vertical Position and Sound Velocity Variation for GNSS/Acoustic Seafloor Geodetic Calibration Based on Moving Survey Data

The accuracy of GNSS/Acoustic seafloor geodetic calibration is greatly influenced by the temporal variation of sound velocity, especially in the vertical direction. Aiming at correcting of the unknown parameters related to both the positions and the sound velocity, this paper proposes a step-by-step inversion scheme based on moving survey data. The proposed method firstly estimates the horizontal normalized travel time delay with sound ray tracing strategy and then computes the horizontal position with circle line observations. We reconstructed an inversion scheme for extracting the surface sound velocity disturbance (SSVD) and corrected the vertical position from cross line data. The SSVD is decomposed into a sum of different period disturbances, and a new SSVD is reconstructed by combining the long period disturbance and short period disturbance. The proposed algorithm is verified by the South China Sea experiment for GNSS/Acoustic seafloor geodetic calibration. The results demonstrate that the new method can take the effects of sound velocity variation into consideration and improve the precision of the vertical position, which is superior to the least squares (LS), the single-difference LS for seafloor geodetic calibration.