A diminished North Atlantic nutrient stream during Younger Dryas climate reversal.

The high rate of biological productivity in the North Atlantic is stimulated by the advective supply of nutrients into the region via the Gulf Stream (nutrient stream). It has been proposed that the projected future decline in the Atlantic Meridional Overturning Circulation (AMOC) will cause a reduction in nutrient supply and resulting productivity. In this work, we examine how the nutrient stream changed over the Younger Dryas climate reversal that marked the transition out of the last ice age. Gulf Stream nutrient content decreased, and oxygen content increased at the Florida Straits during this time of weakened AMOC. The decreased nutrient stream was accompanied by a reduction in biological productivity at higher latitudes in the North Atlantic, which supports the link postulated in theoretical and modeling studies.

Microcystin-LR Induces Estrogenic Effects at Environmentally Relevant Concentration in Black-Spotted Pond Frogs (Pelophylax nigromaculatus): In Situ, In Vivo, In Vitro, and In Silico Investigations.

Harmful cyanobacterial blooms are frequent and intense worldwide, creating hazards for aquatic biodiversity. The potential estrogen-like effect of Microcystin-LR (MC-LR) is a growing concern. In this study, we assessed the estrogenic potency of MC-LR in black-spotted frogs through combined field and laboratory approaches. In 13 bloom areas of Zhejiang province, China, the MC-LR concentrations in water ranged from 0.87 to 8.77 µg/L and were correlated with sex hormone profiles in frogs, suggesting possible estrogenic activity of MC-LR. Tadpoles exposed to 1 µg/L, an environmentally relevant concentration, displayed a female-biased sex ratio relative to controls. Transcriptomic results revealed that MC-LR induces numerous and complex effects on gene expression across multiple endocrine axes. In addition, exposure of male adults significantly increased the estradiol (E2)/testosterone (T) ratio by 3.5-fold relative to controls. Downregulation of genes related to male reproductive endocrine function was also identified. We also showed how MC-LR enhances the expression of specific estrogen receptor (ER) proteins, which induce estrogenic effects by activating the ER pathway and hypothalamic-pituitary-gonadal (HPG) axis. In aggregate, our results reveal multiple lines of evidence demonstrating that, for amphibians, MC-LR is an estrogenic endocrine disruptor at environmentally relevant concentrations. The data presented here support the need for a shift in the MC-LR risk assessment. While hepatoxicity has historically been the focus of MC-LR risk assessments, our data clearly demonstrate that estrogenicity is a major mode of toxicity at environmental levels and that estrogenic effects should be considered for risk assessments on MC-LR going forward.

Does salinity mediate the toxicity of perfluorooctanesulfonic acid (PFOS) in an estuarine fish?

Perfluorooctanesulfonic acid (PFOS) is detected in estuarine environments, where salinity levels fluctuate regularly. We investigated the effects of salinity on the toxicity of PFOS in embryos and larvae of Cyprinodon variegatus. We crossed six PFOS treatments (0, 1-10,000 µg/L) with two salinities (10, 30 ppt). Larvae exposed to the highest concentration of PFOS under high salinity accumulated over twice the amount of PFOS compared to larvae maintained under low salinity. Embryonic survival was unaffected by PFOS, salinity, or their interaction. PFOS delayed time to hatch and increased salinity reduced time to hatch regardless of PFOS treatment; however, no salinity by PFOS interactions were observed. Conversely, PFOS and salinity interacted in the larval stage, with decreased survival at 30 ppt salinity. This is one of the first studies evaluating interactive effects of PFOS and high salinity and highlights the importance of assessing PFAS toxicity across life stages.

Effects of Photobiomodulation on Pain and Return to Play of Injured Athletes: A Systematic Review and Meta-analysis.

ABSTRACT: Morgan, RM, Wheeler, TD, Poolman, MA, Haugen, ENJ, LeMire, SD, and Fitzgerald, JS. Effects of photobiomodulation on pain and return to play of injured athletes: A systematic review and meta-analysis. J Strength Cond Res 38(6): e310-e319, 2024-The aims of this systematic review and meta-analysis were to evaluate the effect of photobiomodulation (PBM) on musculoskeletal pain in injured athletes and to determine if the effects of PBM allowed injured athletes to return to play faster. Electronic databases (MEDLINE Complete, CINAHL, and SPORTDiscus, PubMed, Web of Science, and Embase) were systematically searched (up to and including November 7, 2023) for peer-reviewed randomized controlled trials (RCTs) meeting criteria. Six RCTs, representing 205 competitive and recreational athletes with a mean age of 24 years, were included in the analysis. There were 6 intervention groups using standard physical therapy (n = 1), placebo PBM (n = 4), and aloe gel (n = 1) lasting between 10 minutes and 8 weeks in duration. The level of significance set for the study was p < 0.05. Overall, the use of PBM indicated a positive effect on pain reduction for PBM vs. control groups, standardized mean differences = 1.03, SE = 0.22, 95% confidence intervals = [0.43-1.63], p = 0.0089, but the 2 RCTs found evaluating the effect of PBM on time to return to play after injury in athletes do not support a benefit. Allied healthcare professionals may use PBM to reduce pain, thus allowing an athlete to return to their normal biomechanical movement faster; however, limited evidence suggests that PBM does not reduce time to return to play after an injury.

Lead Speciation, Bioaccessibility, and Sources for a Contaminated Subset of House Dust and Soils Collected from Similar United States Residences.

Residential lead (Pb) exposure is of critical concern to families globally as Pb promotes severe neurological effects in children, especially those less than 5 years old, and no blood lead level is deemed safe by the US Center for Disease Control. House dust and soils are commonly thought to be important sources of Pb exposure. Probing the relationship between house dust and soil Pb is critical to understanding residential exposure, as Pb bioavailability is highly influenced by Pb sources and/or species. We investigated paired house dust and soil collected from homes built before 1978 to determine Pb speciation, source, and bioaccessibility with the primary goal of assessing chemical factors driving Pb exposure in residential media. House dust was predominately found to contain (hydro)cerussite (i.e., Pb (hydroxy)carbonate) phases commonly used in Pb-based paint that, in-turn, promoted elevated bioaccessibility (>60%). Pb X-ray absorption spectroscopy, µ-XRF mapping, and Pb isotope ratio analysis for house dust and soils support house dust Pb as chemically unique compared to exterior soils, although paint Pb is expected to be a major source for both. Soil pedogenesis and increased protection from environmental conditions (e.g., weathering) in households is expected to greatly impact Pb phase differences between house dust and soils, subsequently dictating differences in Pb exposure.

Decadal changes in biomass and distribution of key fisheries species on Newfoundland's Grand Banks.

Canadian fisheries management has embraced the precautionary approach and the incorporation of ecosystem information into decision-making processes. Accurate estimation of fish stock biomass is crucial for ensuring sustainable exploitation of marine resources. Spatio-temporal models can provide improved indices of biomass as they capture spatial and temporal correlations in data and can account for environmental factors influencing biomass distributions. In this study, we developed a spatio-temporal generalized additive model (st-GAM) to investigate the relationships between bottom temperature, depth, and the biomass of three key fished species on The Grand Banks: snow crab (Chionoecetes opilio), yellowtail flounder (Limanda ferruginea), and Atlantic cod (Gadus morhua). Our findings revealed changes in the centre of gravity of Atlantic cod that could be related to a northern shift of the species within the Grand Banks or to a faster recovery of the 2J3KL stock. Atlantic cod also displayed hyperaggregation behaviour with the species showing a continuous distribution over the Grand Banks when biomass is high. These findings suggest a joint stock assessment between the 2J3KL and 3NO stocks would be advisable. However, barriers may need to be addressed to achieve collaboration between the two distinct regulatory bodies (i.e., DFO and NAFO) in charge of managing the stocks. Snow crab and yellowtail flounder centres of gravity have remained relatively constant over time. We also estimated novel indices of biomass, informed by environmental factors. Our study represents a step towards ecosystem-based fisheries management for the highly dynamic Grand Banks.

Advancing Treatment in Atopic Dermatitis: A Comprehensive Review of Clinical Efficacy, Safety, and Comparative Insights Into Corticosteroids, Calcineurin Inhibitors, and Phosphodiesterase-4 Inhibitors as Topical Therapies.

Atopic dermatitis (AD) is a pervasive and multifaceted dermatological disorder causing daily distress to afflicted individuals worldwide. This comprehensive review synthesizes the historical and contemporary advancements in therapeutic strategies, offering a critical analysis of their efficacy, safety profiles, and adaptability. The enduring role of topical corticosteroids in managing AD is examined, acknowledging their potent anti-inflammatory properties alongside their potential adverse side effects, particularly in extended usage. The article explores the utilization of topical calcineurin inhibitors like tacrolimus and pimecrolimus, highlighting their novel anti-inflammatory pathways while also scrutinizing concerns over potential malignancies that relegate them to second-line therapy. The present investigation features the emergence of crisaborole, a phosphodiesterase four inhibitor. Its innovative mode of action, benign safety profile, and applicability to mild and moderate AD are thoroughly evaluated. The review also includes challenges, particularly cost considerations, which constrain accessibility and necessitate nuanced implementation in therapeutic regimens. This study underscores the need for persistent investigation, teamwork, and innovations in managing AD. In this regard, AD requires a united approach between clinicians, researchers, affected individuals, and policymakers to refine patient-focused treatment and develop precise, economical strategies to address this chronic and frequently life-altering health condition.

Protein mimetic 2D FAST rescues alpha synuclein aggregation mediated early and post disease Parkinson's phenotypes.

Abberent protein-protein interactions potentiate many diseases and one example is the toxic, self-assembly of α-Synuclein in the dopaminergic neurons of patients with Parkinson's disease; therefore, a potential therapeutic strategy is the small molecule modulation of α-Synuclein aggregation. In this work, we develop an Oligopyridylamide based 2-dimensional Fragment-Assisted Structure-based Technique to identify antagonists of α-Synuclein aggregation. The technique utilizes a fragment-based screening of an extensive array of non-proteinogenic side chains in Oligopyridylamides, leading to the identification of NS132 as an antagonist of the multiple facets of α-Synuclein aggregation. We further identify a more cell permeable analog (NS163) without sacrificing activity. Oligopyridylamides rescue α-Synuclein aggregation mediated Parkinson's disease phenotypes in dopaminergic neurons in early and post disease Caenorhabditis elegans models. We forsee tremendous potential in our technique to identify lead therapeutics for Parkinson's disease and other diseases as it is expandable to other oligoamide scaffolds and a larger array of side chains.

Abatacept decreases renal T-cell infiltration and renal inflammation and ameliorates progressive renal injury in obese Dahl salt-sensitive rats before puberty.

ABSTRACT: Prepubertal obesity (PPO) is growing at an alarming rate and is now considered a risk factor for renal injury. Recently, we reported that the early development of renal injury in obese Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) rats was associated with increased T-cell infiltration and activation prior to puberty. Therefore, the current study investigated the effect of inhibiting T-cell activation with abatacept on the progression of renal injury in young obese SSLepRmutant rats before puberty. Four-week-old SS and SSLepRmutant rats were treated with IgG or abatacept (1 mg/kg; ip, every other day) for 4 weeks. Abatacept reduced the renal infiltration of T-cells by almost 50% in SSLepRmutant rats. Treatment with abatacept decreased the renal expression of macrophage inflammatory protein-3 alpha (MIP-3α) while increasing IL-4 in SSLepRmutant rats without affecting SS rats. While not having an impact on blood glucose, abatacept reduced hyperinsulinemia and plasma triglycerides in SSLepRmutant rats without affecting SS rats. We did not observe any differences in MAP among the groups. Proteinuria was markedly higher in SSLepRmutant rats versus SS rats throughout the study, and treatment with abatacept decreased proteinuria by about 40% in SSLepRmutant rats without affecting SS rats. We observed significant increases in glomerular and tubular injury and renal fibrosis in SSLepRmutant rats vs SS rats, and chronic treatment with abatacept significantly reduced these renal abnormalities in SSLepRmutant rats. These data suggest that renal T-cell activation contributes to the early progression of renal injury associated with PPO.

United States house dust Pb concentrations are influenced by soil, paint, and house age: insights from a national survey.

BACKGROUND: Lead (Pb) in house dust contributes significantly to blood lead levels (BLLs) in children which may result in dire health consequences. Assessment of house dust Pb in the United States, relationships with Pb in soil and paint, and residential factors influencing Pb concentrations are essential to probing drivers of house dust Pb exposure. OBJECTIVE: Pb concentrations in vacuum-collected house dust are characterized across 346 homes participating in the American Health Homes Survey II (AHHS II), a US survey (2018-2019) evaluating residential Pb hazards. Connections between house dust Pb and soil Pb, paint Pb, and other residential factors are evaluated, and dust Pb concentration data are compared to paired loading data to understand Pb hazard standard implications. RESULTS: Mean and median vacuum dust Pb concentrations were 124 µg Pb g-1 and 34 µg Pb g-1, respectively. Vacuum-collected dust concentrations and dust wipe Pb loading rates were significantly correlated within homes (α < 0.001; r ≥ 0.4). At least one wipe sample exceeded current house dust Pb loading hazard standards (10 µg ft-2 or 100 µg Pb ft-2 for floors and windowsills, respectively) in 75 of 346 homes (22%). House dust Pb concentrations were correlated with soil Pb (r = 0.64) and Pb paint (r = 0.57). Soil Pb and paint Pb were also correlated (r = 0.6). IMPACT: The AHHS II provides a window into the current state of Pb in and around residences. We evaluated the relationship between house dust Pb concentrations and two common residential Pb sources: soil and Pb-based paint. Here, we identify relationships between Pb concentrations from vacuum-collected dust and paired Pb wipe loading data, enabling dust Pb concentrations to be evaluated in the context of hazard standards. This relationship, along with direct ties to Pb in soil and interior/exterior paint, provides a comprehensive assessment of dust Pb for US homes, crucial for formulating effective strategies to mitigate Pb exposure risks in households.

Simultaneous Spin Coating and Ring-Opening Metathesis Polymerization for the Rapid Synthesis of Polymer Films.

We report a highly controlled technique for the synthesis of polymer films atop a substrate by combining spin coating with ring-opening metathesis polymerization (ROMP), herein termed spin coating ROMP (scROMP). The scROMP approach combines polymer synthesis and deposition into one process, fabricating films of up to 36 cm2 in under 3 min with orders-of-magnitude reduction in solvent usage. This method can convert numerous norbornene-type molecules into homopolymers and random copolymers as uniform films on both porous and nonporous substrates. Film thickness can be varied from a few hundred nanometers to a few tens of micrometers based on spin speed and monomer concentration. The resulting polymers possess high MW (>100 kDa) and low polydispersity (PDI) (<1.2) values that are similar to ROMP polymers made in solution. We also devise a model to investigate the balance between convective monomer spin-off and polymer growth from the surface, which allows the determination of critical kinetic parameters for scROMP. Finally, translation of scROMP to porous supports enables the synthesis of thin film composite membranes that demonstrate the ability to dehydrate ethanol by pervaporation.

Effects of running skill and speed on limb coordination during submaximal and maximal sprinting.

In locomotion, the relative phasing of the limbs changes with speed and provides valuable insight to neuromuscular control of gait. At present, it is unknown if individuals trained in sprinting coordinate their limbs differently than runners from other athletic backgrounds. Therefore, we aimed to characterize the effects of speed and skill on lower limb coordination. Twenty-five physically active (PA) and fifteen track and field (TF) athletes performed 40 m running trials at self-selected speeds, from jogging to maximal sprinting. We measured lower limb kinematics during steady-speed running, and quantified coordination using continuous relative phase (CRP) methods for interlimb pairs (Thigh-Thigh, Shank-Shank) and intralimb pairs (Shank-Thigh). Regression techniques showed between-group differences in scaling of coordination with speed during the stance phase, such that coordination was significantly more antiphase during jogging and running speeds in TF. During flight the scaling between groups was similar, but there were persistent and significant differences in coordination across all speeds. Comparing only the maximal speed trials, we found interlimb coordination was significantly more antiphase for TF in both stance and flight. In all cases, Shank-Shank coordination showed the largest between-group differences. Our results demonstrate the importance of interlimb coordination at maximal sprint speed, particularly during the flight phase and between shank segments. Between-group differences in coordination at slower speeds suggest a selective tuning of coordination in trained runners. We speculate differences in limb coordination are due to acquired motor patterns from optimizing forward velocity and its mechanical determinants, which differ particularly during flight/swing and between shank segments.

Transcriptomic analysis using RNA sequencing and phenotypic analysis of Salmonella enterica after acid exposure for different time durations using adaptive laboratory evolution.

Introduction: This study is the final part of a two-part series that delves into the molecular mechanisms driving adaptive laboratory evolution (ALE) of Salmonella enterica in acid stress. The phenotypic and transcriptomic alterations in the acid-evolved lineages (EL) of Salmonella enterica serovar Enteritidis after 70 days of acid stress exposure were analyzed. Materials and methods: The stability of phenotypic changes observed after 70 days in acetic acid was explored after stress removal using a newly developed evolutionary lineage EL5. Additionally, the impact of short-term acid stress on the previously adapted lineage EL4 was also examined. Results: The results indicate that the elevated antibiotic minimum inhibitory concentration (MIC) observed after exposure to acetic acid for 70 days was lost when acid stress was removed. This phenomenon was observed against human antibiotics such as meropenem, ciprofloxacin, gentamicin, and streptomycin. The MIC of meropenem in EL4 on day 70 was 0.094 mM, which dropped to 0.032 mM when removed from acetic acid stress after day 70. However, after stress reintroduction, the MIC swiftly elevated, and within 4 days, it returned to 0.094 mM. After 20 more days of adaptation in acetic acid, the meropenem MIC increased to 0.125 mM. The other human antibiotics that were tested exhibited a similar trend. The MIC of acetic acid in EL4 on day 70 was observed to be 35 mM, which remained constant even after the removal of acetic acid stress. Readaptation of EL4 in acetic acid for 20 more days caused the acetic acid MIC to increase to 37 mM. Bacterial whole genome sequencing of EL5 revealed base substitutions in several genes involved in pathogenesis, such as the phoQ and wzc genes. Transcriptomic analysis of EL5 revealed upregulation of virulence, drug resistance, toxin-antitoxin, and iron metabolism genes. Unstable Salmonella small colony variants (SSCV) of S. Enteritidis were also observed in EL5 as compared to the wild-type unevolved S. Enteritidis. Discussion: This study presents a comprehensive understanding of the evolution of the phenotypic, genomic, and transcriptomic changes in S. Enteritidis due to prolonged acid exposure through ALE.

Perceived delivery of essential yoga properties within in-person and remote weight loss maintenance interventions.

OBJECTIVES: While previous research has utilized remote delivery of yoga interventions, no research has specifically interrogated the effectiveness of remote yoga intervention delivery. In this secondary analysis of weight-maintenance trial data, we examined participant perceptions of essential yoga properties across in-person and remote formats, hypothesizing that perceptions would not differ following remote delivery. METHODS: 24 women with overweight or obesity (34.6±4.1 kg/m2, 48.2±9.9 years) received a 12-week Iyengar yoga intervention (2x/week) following a 3-month behavioral weight loss program. Of 23 participants who completed follow-up questionnaires, 12 received the planned in-person intervention and 11 received a remote intervention (delivered live) due to the COVID-19 pandemic. The Essential Properties of Yoga Questionnaire (EPYQ) was completed online by participants and by the instructors to measure the perceptions of the relative emphasis placed on the essential components of the yoga intervention via 14 subscales. Linear regression models were used to compare perceptions of each EPYQ dimension across in-person and remote delivery methods, as well as between participants and instructors, independent of delivery method. RESULTS: 13 of the 14 subscales did not differ between delivery modalities (p>0.05). Participants perceived more individual attention within in-person yoga (p = 0.003). For both delivery methods, instructors perceived breathwork, restorative postures, and body locks to be incorporated to a lesser degree compared to participants (ß = -1.28, p = 0.003; ß = -1.57, p = 0.019; ß = -1.39, p = 0.036; respectively). No other significant differences across the participant and instructor scores were observed. CONCLUSIONS: Findings provide preliminary support for the use of live remote delivery of yoga, effectively communicating most essential yoga properties when compared to in-person classes. However, participants perceived more individual attention with in-person versus remote delivery; thus, future remote-based yoga interventions may benefit from providing additional individualized feedback.

Predicting Redox Conditions in Groundwater at a National Scale Using Random Forest Classification.

Redox conditions in groundwater may markedly affect the fate and transport of nutrients, volatile organic compounds, and trace metals, with significant implications for human health. While many local assessments of redox conditions have been made, the spatial variability of redox reaction rates makes the determination of redox conditions at regional or national scales problematic. In this study, redox conditions in groundwater were predicted for the contiguous United States using random forest classification by relating measured water quality data from over 30,000 wells to natural and anthropogenic factors. The model correctly predicted the oxic/suboxic classification for 78 and 79% of the samples in the out-of-bag and hold-out data sets, respectively. Variables describing geology, hydrology, soil properties, and hydrologic position were among the most important factors affecting the likelihood of oxic conditions in groundwater. Important model variables tended to relate to aquifer recharge, groundwater travel time, or prevalence of electron donors, which are key drivers of redox conditions in groundwater. Partial dependence plots suggested that the likelihood of oxic conditions in groundwater decreased sharply as streams were approached and gradually as the depth below the water table increased. The probability of oxic groundwater increased as base flow index values increased, likely due to the prevalence of well-drained soils and geologic materials in high base flow index areas. The likelihood of oxic conditions increased as topographic wetness index (TWI) values decreased. High topographic wetness index values occur in areas with a propensity for standing water and overland flow, conditions that limit the delivery of dissolved oxygen to groundwater by recharge; higher TWI values also tend to occur in discharge areas, which may contain groundwater with long travel times. A second model was developed to predict the probability of elevated manganese (Mn) concentrations in groundwater (i.e., ≥50 µg/L). The Mn model relied on many of the same variables as the oxic/suboxic model and may be used to identify areas where Mn-reducing conditions occur and where there is an increased risk to domestic water supplies due to high Mn concentrations. Model predictions of redox conditions in groundwater produced in this study may help identify regions of the country with elevated groundwater vulnerability and stream vulnerability to groundwater-derived contaminants.

Authorship gender among articles about artificial intelligence in breast imaging.

RATIONALE AND OBJECTIVES: The purpose of this study is to investigate the variance of women authors, specifically first and senior authorship among peer-reviewed artificial intelligence-related articles with a specific focus in breast imaging. MATERIALS AND METHODS: A strategic search was conducted in July 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to capture all existing and publicly available peer-reviewed articles intersecting AI and breast imaging. Primary outcomes were first and senior authors' gender, which were assigned with the aid of an emailed self-declaration survey. Secondary outcomes included country of article, journal impact factor, and year of publication. Comparisons were made using logistic regression models and analysis of variances. RESULTS: 115 studies were included in the analysis. Women authors represented 35.7% (41/115) and 37.4% (43/115) of first and senior authors, respectively. Logistic regression modelling showed a significant increase in women senior authors over time but no changes in women first authors. Impact factor was not associated with female authorship and certain countries had women authorship reach over 50%. CONCLUSION: This study demonstrates that there is a significant authorship gender gap in artificial intelligence breast imaging research. An increasing temporal trend of senior authors in breast imaging AI-related research is a promising prognosis for more women voices in this field. Further study needs to be done to understand the reasons behind this gap and any potential implications.

Simulated gastric leachate of 3D printer metal-fill filaments induces cytotoxic effects in rat and human intestinal models.

Metals are used in 3-dimensional (3D) printer filaments in the manufacture of 3D printed objects. Exposure to the filaments, printed objects and emissions from printing may pose health risks from release of toxic metals. This study investigated the cytotoxicity of extruded 3D printer filament leachates in rat and human intestinal cells. Copper-, bronze-, and steel-fill extruded filaments were incubated in acidic media for 2 h. Leachates were adjusted to pH 7 and cells exposed for 4 or 24 h. Concentration- and time-dependent decreases in rat and human cell viability were observed using a colorimetric assay and confirmed by microscopy. Copper- and bronze-fill leachates were more cytotoxic than steel. Copper-fill leachates had the highest copper concentrations by ICP-MS. Exposure to CuSO4 resulted in concentration-dependent cytotoxicity in rat cells. The copper chelator bathocuproine disulphonate alleviated cytotoxicity of CuSO4 and copper-fill leachate, suggesting that copper ions have a role in the cytotoxicity. Hydrogen peroxide increased and glutathione decreased in rat cells exposed to copper-fill leachate, suggesting the formation of reactive oxygen species. Overall, our data indicate that metals released from the acidic exposure of print objects using metal-fill filaments, especially copper, are toxic to rat and human intestinal cells and additional studies are needed.

Achilles Allograft Fiber Track Graft Preparation Technique for Anterior Cruciate Ligament Reconstruction.

Anterior cruciate ligament rupture is a common orthopaedic injury, with reconstruction the treatment of choice for active individuals. Graft selection is an important consideration for surgical planning. Achilles tendon allograft is a graft choice most likely used in cases of revision anterior cruciate ligament reconstruction. This technical note discusses an approach to Achilles tendon allograft preparation that respects and follows the rotation of the fibers of the Achilles tendon. Key considerations in the use of this technique include (1) identifying the rotational fiber tracks, (2) performing careful dissection along the identified tracks of the fibers, and (3) ensuring an appropriate graft width based on patient size, all of which are crucial for the success of this unique technique. The preservation of the rotational fibers provided by this technique may have the potential to result in increased tensile strength and better clinical outcomes.

Cell Cycle-Dependent TICRR/TRESLIN and MTBP Chromatin Binding Mechanisms and Patterns.

The selection of replication origins is a defining characteristic of DNA replication in eukaryotes, yet its mechanism in humans has not been well-defined. In this study, we use Cut&Run to examine genomic binding locations for TICRR/TRESLIN and MTBP, the human orthologs for the yeast DNA replication initiation factors Sld3 and Sld7. We mapped TRESLIN and MTBP binding in HCT116 colorectal cancer cells using asynchronous and G1 synchronized populations. Our data show that TRESLIN and MTBP binding patterns are more defined in a G1 synchronized population compared to asynchronously cycling cells. We also examined whether TRESLIN and MTBP are dependent on one another for binding. Our data suggest MTBP is dependent on TRESLIN for proper association with chromatin during G1 but not S phase. Finally, we asked whether TRESLIN and MTBP binding to chromatin requires licensed origins. Using cell lines with a non-degradable inducible Geminin to inhibit licensing, we show TRESLIN and MTBP binding does not require loaded MCMs. Altogether, our Cut&Run data provides evidence for a chromatin binding mechanism of TRESLIN-MTBP during G1 that is dependent on TRESLIN and does not require interactions with licensed origins.