Identification Drug Targets for Oxaliplatin-Induced Cardiotoxicity without Affecting Cancer Treatment through Inter Variability Cross-Correlation Analysis (IVCCA).

The successful treatment of side effects of chemotherapy faces two major limitations: the need to avoid interfering with pathways essential for the cancer-destroying effects of the chemotherapy drug, and the need to avoid helping tumor progression through cancer promoting cellular pathways. To address these questions and identify new pathways and targets that satisfy these limitations, we have developed the bioinformatics tool Inter Variability Cross-Correlation Analysis (IVCCA). This tool calculates the cross-correlation of differentially expressed genes, analyzes their clusters, and compares them across a vast number of known pathways to identify the most relevant target(s). To demonstrate the utility of IVCCA, we applied this platform to RNA-seq data obtained from the hearts of the animal models with oxaliplatin-induced CTX. RNA-seq of the heart tissue from oxaliplatin treated mice identified 1744 differentially expressed genes with False Discovery Rate (FDR) less than 0.05 and fold change above 1.5 across nine samples. We compared the results against traditional gene enrichment analysis methods, revealing that IVCCA identified additional pathways potentially involved in CTX beyond those detected by conventional approaches. The newly identified pathways such as energy metabolism and several others represent promising target for therapeutic intervention against CTX, while preserving the efficacy of the chemotherapy treatment and avoiding tumor proliferation. Targeting these pathways is expected to mitigate the damaging effects of chemotherapy on cardiac tissues and improve patient outcomes by reducing the incidence of heart failure and other cardiovascular complications, ultimately enabling patients to complete their full course of chemotherapy with improved quality of life and survival rates.

The Diversity of Wolbachia across the Turtle Ants (Formicidae: Cephalotes spp.).

Wolbachia is a widespread and well-known bacterium that can induce a wide range of changes within its host. Ants specifically harbor a great deal of Wolbachia diversity and are useful systems to study endosymbiosis. The turtle ants (Cephalotes) are a widespread group of tropical ants that rely on gut microbes to support their herbivorous diet for their survival, yet little is known of the extent of this diversity. Therefore, studying their endosymbionts and categorizing the diversity of bacteria within Cephalotes hosts could help to delimit species and identify new strains and can help lead to a further understanding of how the microbiome leads to survival and speciation in the wild. In our study, 116 individual samples were initially tested for positive infection with the wsp gene. Of the initial 116 samples, 9 samples were infected with only one strain of Wolbachia, and 7 were able to be used successfully for multilocus sequence typing (MLST). We used the new MLST data to infer a phylogeny with other Formicidae samples from the MLST online database to identify new Wolbachia strains and related genes, of which only one came back as an exact match. The 18 Wolbachia-positive samples ranged across 15 different species and 7 different countries, which we further test for species identity and geographic correlation. This study is the first comprehensive look into the diversity of Wolbachia in the turtle ants, providing insight into how endosymbionts are oriented in widespread species and providing a strong foundation for further research in host-microbe interactions.

DRG Explant Model: Elucidating Mechanisms of Oxaliplatin-Induced Peripheral Neuropathy and Identifying Potential Therapeutic Targets.

Oxaliplatin triggered chemotherapy induced peripheral neuropathy (CIPN) is a common and debilitating side effect of cancer treatment which limits the efficacy of chemotherapy and negatively impacts patients quality of life dramatically. For better understanding the mechanisms of CIPN and screen for potential therapeutic targets, it is critical to have reliable in vitro assays that effectively mirror the neuropathy in vivo . In this study, we established a dorsal root ganglia (DRG) explant model. This model displayed dose-dependent inhibition of neurite outgrowth in response to oxaliplatin, while oxalic acid exhibited no significant impact on the regrowth of DRG. The robustness of this assay was further demonstrated by the inhibition of OCT2 transporter, which facilitates oxaliplatin accumulation in neurons, fully restoring the neurite regrowth capacity. Using this model, we revealed that oxaliplatin triggered a substantial increase of oxidative stress in DRG. Notably, inhibition of TXNIP with verapamil significantly reduced oxidative stress level. Our results demonstrated the use of DRG explants as an efficient model to study the mechanisms of CIPN and screen for potential treatments.

Oxaliplatin-induced cardiotoxicity in mice is connected to the changes in energy metabolism in the heart tissue.

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. At high cumulative dosage, the negative effect of oxaliplatin on the heart becomes evident and is linked to a growing number of clinical reports. The aim of this study was to determine how chronic oxaliplatin treatment causes the changes in energy-related metabolic activity in the heart that leads to cardiotoxicity and heart damage in mice. C57BL/6 male mice were treated with a human equivalent dosage of intraperitoneal oxaliplatin (0 and 10 mg/kg) once a week for eight weeks. During the treatment, mice were followed for physiological parameters, ECG, histology and RNA sequencing of the heart. We identified that oxaliplatin induces strong changes in the heart and affects the heart's energy-related metabolic profile. Histological post-mortem evaluation identified focal myocardial necrosis infiltrated with a small number of associated neutrophils. Accumulated doses of oxaliplatin led to significant changes in gene expression related to energy related metabolic pathways including fatty acid (FA) oxidation, amino acid metabolism, glycolysis, electron transport chain, and NAD synthesis pathway. At high accumulative doses of oxaliplatin, the heart shifts its metabolism from FAs to glycolysis and increases lactate production. It also leads to strong overexpression of genes in NAD synthesis pathways such as Nmrk2. Changes in gene expression associated with energy metabolic pathways can be used to develop diagnostic methods to detect oxaliplatin-induced cardiotoxicity early on as well as therapy to compensate for the energy deficit in the heart to prevent heart damage.

Climate change mitigation potential of Louisiana's coastal area: Current estimates and future projections.

Coastal habitats can play an important role in climate change mitigation. As Louisiana implements its climate action plan and the restoration and risk-reduction projects outlined in its 2017 Louisiana Coastal Master Plan, it is critical to consider potential greenhouse gas (GHG) fluxes in coastal habitats. This study estimated the potential climate mitigation role of existing, converted, and restored coastal habitats for years 2005, 2020, 2025, 2030, and 2050, which align with the Governor of Louisiana's GHG reduction targets. An analytical framework was developed that considered (1) available scientific data on net ecosystem carbon balance fluxes per habitat and (2) habitat areas projected from modeling efforts used for the 2017 Louisiana Coastal Master Plan to estimate the net GHG flux of coastal area. The coastal area was estimated as net GHG sinks of -38.4 ± 10.6 and -43.2 ± 12.0 Tg CO2 equivalents (CO2 e) in 2005 and 2020, respectively. The coastal area was projected to remain a net GHG sink in 2025 and 2030, both with and without the implementation of Coastal Master Plan projects (means ranged from -25.3 to -34.2 Tg CO2 e). By 2050, with model-projected wetland loss and conversion of coastal habitats to open water due to coastal erosion and relative sea level rise, Louisiana's coastal area was projected to become a net source of GHG emissions both with and without the Coastal Master Plan projects. However, in the year 2050, the Louisiana Coastal Master Plan project implementation was projected to avoid the release of +8.8 ± 1.3 Tg CO2 e compared with an alternative with no action. Reduction in current and future stressors to coastal habitats, including impacts from sea level rise, as well as the implementation of restoration projects could help to ensure coastal areas remain a natural climate solution.

Trends in Surgical Approach for Single-Level Lumbar Fusion Over the Past Decade.

STUDY DESIGN: Retrospective Comparative Study. OBJECTIVE: The purpose of this study was to characterize trends in surgical approach for single-level lumbar fusion over the past decade. SUMMARY OF BACKGROUND DATA: The number of elective lumbar fusion cases performed is increasing annually. Several different surgical approaches exist for lumbar spinal fusion including novel anterior approaches developed in recent years. With ongoing innovation, trends in the utilization of common surgical approaches in recent years are unclear. MATERIALS AND METHODS: A retrospective cohort study was conducted using the PearlDiver database (Fort Wayne, IN). Patients undergoing single-level lumbar fusion between 2010 and 2019 were identified using Current Procedural Technology codes and divided into 4 mutually exclusive cohorts based on surgical approach: (1) anterior-only, (2) anterior approach with posterior instrumentation, (3) posterolateral, and (4) posterior-only interbody. Trend analyses of surgical approach utilization over the last decade were performed with the Cochran-Armitage test to evaluate the 2-tailed null hypothesis that utilization of each surgical approach for single-level lumbar fusion remained constant. RESULTS: A total of 53,234 patients met inclusion criteria and were stratified into 4 cohorts: anterior-only (n=5104), anterior with posterior instrumentation (n=23,515), posterolateral (n=5525), and posterior-only interbody (n=19,090). Trend analysis revealed the utilization of a posterior-only interbody approach significantly decreased from 36.7% to 29.2% ( P <0.001), whereas the utilization of a combined anterior and posterior approach significantly increased from 45.8% to 50.4% ( P <0.001). The utilization of an anterior-only approach also significantly increased from 7.9% to 10.5% ( P <0.001). CONCLUSIONS: Utilization of anterior-only and anterior with posterior instrumentation approaches for single-level lumbar fusion have been significantly increasing over the past decade while use of posterior-only interbody approach trended significantly downward. These data may be particularly useful for trainees and spine surgeons as new techniques and technology become available. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Employing micro-aeration in anaerobic digestion of poultry litter and wheat straw: Batch kinetics and continuous performance.

In this study, different micro-aeration (MA) strategies for anaerobic digestion (AD) of poultry litter (PL) and wheat straw (WS) were examined. MA at different stages (pretreatment, middle, pretreatment plus middle, and daily) in batch AD of WS showed that daily MA had the highest increase (16.5 %) of the cumulative methane yield (CMY) compared to the control. Batch co-digestion (Co-AD) of WS and PL with daily MA obtained a furtherly improved (15.1 %) CMY of 225.44 N mL CH4/g vS added. The modified Gompertz model and Cone model were good in fitting the methane yield kinetics of MA engaged AD process (R2 greater than 0.99). Daily MA shortened the lag phase of Co-AD by 3.4 %. The sequencing batch reactor for the Co-AD of WS and PL showed an increased (21.5 %) daily methane yield when 0.5-h/d MA was employed. The results provided support for the application of micro-aeration in the AD of agricultural wastes.

Identifying the Role of Elevation, Geography, and Species Identity in Structuring Turtle Ant (Cephalotes Latreille, 1802) Bacterial Communities.

Bacterial communities in animals are often necessary for hosts to survive, particularly for hosts with nutrient-limited diets. The composition, abundance, and richness of these bacterial communities may be shaped by host identity and external ecological factors. The turtle ants (genus Cephalotes) are predominantly herbivorous and known to rely on bacterial communities to enrich their diet. Cephalotes have a broad Neotropical distribution, with high diversity in the South American Cerrado, a geologically and biologically diverse savanna. Using 16S rRNA amplicon sequencing, we examined the bacterial communities of forty-one Cephalotes samples of sixteen different species collected from multiple locations across two sites in the Cerrado (MG, Brazil) and compared the bacterial communities according to elevation, locality, species, and species group, defined by host phylogeny. Beta diversity of bacterial communities differed with respect to all categories but particularly strongly when compared by geographic location, species, and species group. Differences seen in species and species groups can be partially explained by the high abundance of Mesorhizobium in Cephalotes pusillus and Cephalotes depressus species groups, when compared to other clades via the Analysis of Composition of Microbiome (ANCOM). Though the Cephalotes bacterial community is highly conserved, results from this study indicate that multiple external factors can affect and change bacterial community composition and abundance.

Anterior lumbar spinal fusion surgery associated with lower risk of stroke, pneumonia, and infection compared to posterior lumbar spinal fusion surgery.

Background: Prior studies, comparing anterior and posterior approaches to lumbar fusion surgery, found similar fusion rates and clinical outcomes, but are limited by sample size. Further evaluation of the postoperative complications of each approach is necessary. Methods: The MSpine database by PearlDiver was queried using ICD-9, ICD-10, and CPT codes to identify patients who had undergone single-level anterior or posterior lumbar interbody fusion surgery. Readmission rates, ileus, lower extremity DVT, infection, pneumonia, and stroke were used to compare post-operative complications of an anterior vs. posterior approach. Results: 112,023 patients were included in this study, with 38,529 (34.4%) in the anterior group (ALIF/LLIF) and 73,494 (65.6%) in the posterior group (PLIF/TLIF). At both 30 and 90-days postoperative, patients undergoing an anterior approach to lumbar interbody fusion had a higher odds ratio of lower extremity DVT (30-day OR: 1.19, 90-day OR: 1.16; P<0.05) and ileus complication (30-day OR: 1.87, P= <.05; 90-day OR: 1.81, P<.05). At both 30 and 90-days postoperative, patients undergoing a posterior approach had a higher odds ratio of stroke (30-day: OR: 0.79, 90-day OR: 0.87; P<0.05), transfusion (30-day OR: 0.66, 90-day OR: 0.69; P<.05), infection (30-day OR: 0.88, 90-day OR: 0.91; P <.05), and pneumonia (30-day OR: 0.85, 90-day OR: 0.90; P<.05). There was no statistically significant difference in myocardial infarction or pulmonary embolism between both approaches at 30 and 90-days postoperative. Conclusions: Anterior and posterior approaches for lumbar interbody fusion were associated with differences in postoperative complications at 30 and 90-days. The complication profiles associated with each approach can inform surgeon treatment decisions based on patient profiles.

Isotopic evidence that aestivation allows malaria mosquitoes to persist through the dry season in the Sahel.

Data suggest that the malaria vector mosquito Anopheles coluzzii persists during the dry season in the Sahel through a dormancy mechanism known as aestivation; however, the contribution of aestivation compared with alternative strategies such as migration is unknown. Here we marked larval Anopheles mosquitoes in two Sahelian villages in Mali using deuterium (2H) to assess the contribution of aestivation to persistence of mosquitoes through the seven-month dry season. After an initial enrichment period, 33% of An. coluzzii mosquitoes were strongly marked. Seven months following enrichment, multiple analysis methods supported the ongoing presence of marked mosquitoes, compatible with the prediction that the fraction of marked mosquitoes should remain stable throughout the dry season if local aestivation is occurring. The results suggest that aestivation is a major persistence mechanism of An. coluzzii in the Sahel, contributing at least 20% of the adults at the onset of rains. This persistence strategy could influence mosquito control and malaria elimination campaigns.

Trends of single-level anterior cervical discectomy and fusion documentation after the 2015 Centers for Medicare & Medicaid Services coding audit.

OBJECTIVE: With the use of anterior cervical discectomy and fusion (ACDF) expected to rise by 13.3% from 2020 to 2040, the increased usage of interbody cages with integral anterior fixation prompted a Centers for Medicare & Medicaid Services (CMS) review, which resulted in coding changes affecting anterior instrumentation documentation. CMS determined that Current Procedural Terminology (CPT) code 22845 should not be used to report integrated instrumentation (plate) with an interbody device, and if additional anterior instrumentation (e.g., plates and screws) is placed with an integrated interbody device, then a 59 modifier should be used. There is sparse literature examining the trends of ACDF without and with additional anterior instrumentation after the 2015 CMS audit. Therefore, this study aimed to evaluate the trends of single-level subaxial ACDF utilization from 2011 to 2019 to determine whether the 2015 CMS audit influenced the documented usage of additional anterior instrumentation. METHODS: A retrospective cohort study was performed using the commercially available database PearlDiver. Patient records were queried from 2011 to 2019 for single-level subaxial ACDF without (CPT code 22551) and with (CPT codes 22551 + 22845) instrumentation. Cochran-Armitage trend analyses were performed to evaluate the hypothesis that ACDF with additional anterior instrumentation decreased over the given time period. RESULTS: Between 2011 and 2019, the total number of single-level ACDFs decreased from 6202 to 4402. From 2011 to 2015, an average of 6240 patients per year underwent single-level subaxial ACDF; of those, 950 patients (15.2%) had ACDF without instrumentation and 5290 patients (84.8%) had ACDF with instrumentation. In 2016, the total number of single-level subaxial ACDFs decreased to 5525, with 1006 patients (18.2%) receiving no instrumentation and 4519 patients (81.8%) receiving instrumentation. From 2017 to 2019, an average of 4283 patients per year underwent a single-level subaxial ACDF; of these, 1280 (29.9%) had no instrumentation and 3003 (70.1%) had instrumentation (all p < 0.0001). CONCLUSIONS: From 2015 to 2019, single-level ACDF without instrumentation significantly increased by 91.5% and ACDF with anterior instrumentation significantly decreased by 18.1%. The 2015 CMS audit of interbody cages and anterior instrumentation coding (CPT code 22845) may account for the decreased documentation of anterior instrumentation in the 9-year period. Understanding CMS auditing could help surgeons perceive changes in practice patterns that may lead to a more thorough evaluation of patient outcomes, cost, and overall value.

3D Media Stabilizes Membrane and Prolongs Lifespan of Defolliculated Xenopus laevis Oocytes.

Xenopus laevis oocytes are commonly used in many fundamental biological studies. One of the major limitations of X. laevis oocytes is their short storage lifespan with most defolliculated oocytes physically deteriorating in 10 days or less. Herein, we identified a 3D Cultrex-based storage media that incorporates extracellular membrane-based hydrogels to maintain oocyte integrity. Under these treatments, the lifespan of the oocytes increased to more than 20 days compared to standard conditions. The treatment preserved the oocytes membrane integrity and did not interfere with mRNA- or cDNA-derived protein expression.

Far Anterior Medial Portals in Complicated Elbow Arthroscopic Procedures: Safety Profile in a Cadaveric Model.

Purpose: The purpose of this study is to describe the placement and evaluate the safety of the far anterior proximal and distal anteromedial portals by comparing them to previously defined portal techniques in a cadaveric model of the elbow. Methods: Six paired (left and right) fresh, frozen cadaveric elbow joints were dissected. .62-mm Kirschner wires were placed at the literature-defined distal and proximal portal sites on right elbows. The proposed "far anterior" distal and proximal portals were established on the matched left elbows. The elbows were dissected to display the median and ulnar nerves. Digital calipers were used to measure distances from wires to nerves. Results: For the distal portal, the literature-defined portals were a significantly greater distance (P = .014) from the ulnar nerve (31.22 mm) compared to the far anterior portals (24.65 mm). For the proximal portal, the far anterior portals were a significantly greater distance (P = .026) from the ulnar nerve (26.98 mm) than the literature-defined portals (13.75 mm). There was no significant difference between the far anterior and literature-defined proximal and distal portal techniques in relation to the median nerve. Conclusions: Analysis of elbow arthroscopy anteromedial portal technique shows the far, anterior, proximal, and distal portals are a safe distance from the ulnar and median nerves. A portal modification that may address complicated elbow conditions is a more anterior placement of the medial portals to allow for better visualization and access. Clinical Relevance: The elbow is a difficult joint in which to perform arthroscopic surgery. One option our institution has used for safe portal modification to address complicated elbow conditions is a further anterior placement of the medial portals to allow better visualization and access.

Triceps Tendon Ruptures: Risk Factors, Treatment, and Rehabilitation.

Triceps tendon ruptures (TTRs) are rare and often occur as a result of falling on an outstretched hand, forceful eccentric contraction, direct trauma to the elbow, or lifting against resistance. TTRs are most commonly seen in middle-aged men, football players, and weightlifters. Radiography, ultrasonography, and magnetic resonance imaging may be utilized for diagnosis and to guide treatment. Acute partial TTRs may have good outcomes with nonoperative management. Surgery should be considered if nonoperative treatment is unsuccessful or if substantial musculotendinous retraction is present. Surgical repair is strongly recommended for complete TTRs.

New in vitro highly cytotoxic platinum and palladium cyanoximates with minimal side effects in vivo.

Several biologically active bivalent Pd and Pt complexes with two structurally similar cyanoxime ligands abbreviated as H(DECO): 2-oximino-2-cyano-N,N'-diethylacetamide, and H(PyrCO): 2-oximino-2-cyan-N-pyrrolidine acetamide were synthesized and characterized using spectroscopic methods, thermal analysis and X-ray crystallography. Structures revealed planar cis-geometry of studied complexes. Freshly obtained Pt(DECO)2, Pd(DECO)2, Pt(PyrCO)2 and Pd(PyrCO)2 complexes were used in for in vitro cytotoxicity assays using two different etiology human cancer cell lines HeLa and WiDr cells. Investigated compounds showed cytotoxicity levels at or above cisplatin. Pt(DECO)2 was also tested in vivo in healthy C57BL/6 mice. The complex was administered at three different dosage (0, 7.5, 15 mg/kg, i.p. once/week), over a total period of 8 weeks. No changes were observed in the animal weight in the treated mice compared to the control dextrose-treated group. The levels of erythrocytes, leukocytes, and hemoglobin were within the normal level suggesting low myelotoxicity. Negligible cardiotoxicity was observed from the histological evaluation of the hearts from the treated animals. Results from the tail nerve conduction velocity (NCV) and nerve histomorphometry suggested no impact of Pt(DECO)2 on peripheral nerves. The complex, however, induced certain hepatotoxicity and lead to the elevation of IL-6, a pro-inflammatory cytokine. Overall, Pt(DECO)2 showed minimal in vivo toxicity, thus presenting a promising candidate for future testing in animal models of cancer.

Using Xenopus oocytes in neurological disease drug discovery.

Introduction: Neurological diseases present a difficult challenge in drug discovery. Many of the current treatments have limited efficiency or result in a variety of debilitating side effects. The search of new therapies is of a paramount importance, since the number of patients that require a better treatment is growing rapidly. As an in vitro model, Xenopus oocytes provide the drug developer with many distinct advantages, including size, durability, and efficiency in exogenous protein expression. However, there is an increasing need to refine the recent breakthroughs.Areas covered: This review covers the usage and recent advancements of Xenopus oocytes for drug discovery in neurological diseases from expression and functional measurement techniques to current applications in Alzheimer's disease, painful neuropathies, and amyotrophic lateral sclerosis (ALS). The existing limitations of Xenopus oocytes in drug discovery are also discussed.Expert opinion: With the rise of aging population and neurological disorders, Xenopus oocytes, will continue to play an important role in understanding the mechanism of the disease, identification and validation of novel molecular targets, and drug screening, providing high-quality data despite the technical limitations. With further advances in oocytes-related techniques toward an accurate modeling of the disease, the diagnostics and treatment of neuropathologies will be becoming increasing personalized.

DOC export is exceeded by C fixation in May Creek: A late-successional watershed of the Copper River Basin, Alaska.

Understanding the entirety of basin-scale C cycling (DOC fluxes and CO2 exchanges) are central to a holistic perspective of boreal forest biogeochemistry today. Shifts in the timing and magnitude of dissolved organic carbon (DOC) delivery in streams and eventually into oceans can be expected, while simultaneously CO2 emission may exceed CO2 fixation, leading to forests becoming stronger CO2 sources than sinks amplifying rising trace gases in the atmosphere. At May Creek, a representative late-successional boreal forest watershed at the headwaters of the Copper River Basin, Alaska, we quantified the seasonality of DOC flux and landscape-scale CO2 exchange (eddy covariance) over two seasonal cycles. We deployed in situ fDOM and conductivity sensors, performed campaign sampling for water quality (DOC and water isotopes), and used fluorescence spectroscopy to ascertain DOC character. Simultaneously, we quantified net CO2 exchange using a 100 ft eddy covariance tower. Results indicate DOC exports were pulse-driven and mediated by precipitation events. Both frequency and magnitude of pulse-driven DOC events diminished as the seasonal thaw depth deepened, with inputs from terrestrial sources becoming major contributors to the DOC pool with decreasing snowmelt contribution to the hydrograph. A three-component parallel factorial analysis (PARAFAC) model indicated DOC liberated in late-season may be bioavailable (tyrosine-like). Combining Net Ecosystem Exchange (NEE) measurements indicate that the May Creek watershed fixes 142-220 g C m-2 yr-1 and only 0.40-0.57 g C m-2 yr-1 is leached out as DOC. Thus, the May Creek watershed and similar mature spruce forest dominated watersheds in the Copper River Basin are currently large ecosystem C sinks and exceeding C conservative. An understanding of DOC fluxes from Gulf of Alaska watersheds is important for characterizing future climate change-induced seasonal shifts.

Imaging in the repair of peripheral nerve injury.

Surgical intervention followed by physical therapy remains the major way to repair damaged nerves and restore function. Imaging constitutes promising, yet underutilized, approaches to improve surgical and postoperative techniques. Dedicated methods for imaging nerve regeneration will potentially provide surgical guidance, enable recovery monitoring and postrepair intervention, elucidate failure mechanisms and optimize preclinical procedures. Herein, we present an outline of promising innovations in imaging-based tracking of in vivo peripheral nerve regeneration. We emphasize optical imaging because of its cost, versatility, relatively low toxicity and sensitivity. We discuss the use of targeted probes and contrast agents (small molecules and nanoparticles) to facilitate nerve regeneration imaging and the engineering of grafts that could be used to track nerve repair. We also discuss how new imaging methods might overcome the most significant challenges in nerve injury treatment.

Fluorescence lifetime imaging reveals heterogeneous functional distribution of eGFP expressed in Xenopus oocytes.

The oocytes from Xenopus laevis are well known for their polarity, presenting a distinct animal and vegetal pole. Other heterogeneities are less known. To study the heterogeneity of the Xenopus oocyte, we expressed eGFP and analyzed the protein distribution with fluorescence lifetime microscopy. The vegetal pole exhibited higher levels of fluorescence, than the animal pole. However, the fluorescence lifetimes between the two areas were indistinguishable, suggesting similar environments. In contrast, we observed a substantial and gradual decrease in the fluorescence lifetime from 2.9 ns to 2.6 ns as slices approached the periphery. This has an important implication for future oocyte studies as it demonstrates the environment inside the oocyte is not uniform and might affect the fluorescence intensity. As a result, it cannot be assumed that the observed fluorescence intensity reflects the expression of the proteins but might reflect the environment within the oocyte.

European and Mediterranean hydroclimate responses to tropical volcanic forcing over the last millennium.

Volcanic eruptions have global climate impacts, but their effect on the hydrologic cycle is poorly understood. We use a modified version of superposed epoch analysis, an eruption year list collated from multiple datasets, and seasonal paleoclimate reconstructions (soil moisture, precipitation, geopotential heights, and temperature) to investigate volcanic forcing of spring and summer hydroclimate over Europe and the Mediterranean over the last millennium. In the western Mediterranean, wet conditions occur in the eruption year and the following 3 years. Conversely, northwestern Europe and the British Isles experience dry conditions in response to volcanic eruptions, with the largest moisture deficits in post-eruption years 2 and 3. The precipitation response occurs primarily in late spring and early summer (April-July), a pattern that strongly resembles the negative phase of the East Atlantic Pattern. Modulated by this mode of climate variability, eruptions force significant, widespread, and heterogeneous hydroclimate responses across Europe and the Mediterranean.