How Plasmon Ag Nanoparticles can Enhance the Power Performance of a Thermoelectric Generator.

The development of wearable thermoelectric generators (wTEG) represents a promising strategy to replace batteries and supercapacitors required to supply electrical energy for portable electronic devices. However, the main drawback of wTEGs is that the thermal gradient between the skin and the ambient is minimal, reducing the power output produced by the generator. Therefore, it is necessary to improve the thermal management of wTEG in order to increase its efficiency. This work deals with the preparation of a thermoelectric generator that harnesses the plasmonic heating effect to enhance the thermal gradient of the final device. The thermoelectric layer is created through the in situ polymerization of terthiophene (3T) within a polyurethane matrix, utilizing silver (Ag) (I) and copper (II) perchlorate as oxidants. The plasmonic film, composed of Ag-NP (nanoparticles), is formed via photocatalytic reduction of silver nitrate in the presence of titanium oxide. These layers are then meticulously assembled to yield the hybrid plasmonic/thermoelectric generator.

Building a growing genomic data repository for maternal and fetal health through the PING Consortium.

Background: Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Discordant outcomes among dizygotic twins could be explained by genetic susceptibly or protection. Among several well-recognized threats to the developing brain, Zika is a mosquito-borne, positive-stranded RNA virus that was originally isolated in Uganda and spread to cause epidemics in Africa, Asia, and the Americas. In the Americas, the virus caused congenital Zika syndrome and a multitude of neurodevelopmental disorders. As of now, there is no preventative treatment or cure for the adverse outcomes caused by prenatal Zika infection. The Prenatal Infection and Neurodevelopmental Genetics (PING) Consortium was initiated in 2016 to identify factors modulating prenatal brain injury and postnatal neurodevelopmental outcomes for Zika and other prenatal viral infections. Methods: The Consortium has pooled information from eight multi-site studies conducted at 23 research centers in six countries to build a growing clinical and genomic data repository. This repository is being mined to search for modifiers of virally induced brain injury and developmental outcomes. Multilateral partnerships include commitments with Children's National Hospital (USA), Instituto Nacional de Salud (Colombia), the Natural History of Zika Virus Infection in Gestation program (Brazil), and Zika Instituto Fernandes Figueira (Brazil), in addition to the Centers for Disease Control and Prevention and the National Institutes of Health. Discussion: Our goal in bringing together these sets of patient data was to test the hypothesis that personal and populational genetic differences affect the severity of brain injury after a prenatal viral infection and modify neurodevelopmental outcomes. We have enrolled 4,102 mothers and 3,877 infants with 3,063 biological samples and clinical data covering over 80 phenotypic fields and 5,000 variables. There were several notable challenges in bringing together cohorts enrolled in different studies, including variability in the timepoints evaluated and the collected clinical data and biospecimens. Thus far, we have performed whole exome sequencing on 1,226 participants. Here, we present the Consortium's formation and the overarching study design. We began our investigation with prenatal Zika infection with the goal of applying this knowledge to other prenatal infections and exposures that can affect brain development.

Observation of the early stages of environmental contamination in graphene by friction force.

Exposure to ambient air contaminates the surface of graphene sheets. Contamination may arise from different sources, and its nature alters the frictional behavior of the material. These changes in friction enable the observation of the early stages of contaminants' adsorption in graphene. Using a friction force microscope, we show that molecular adsorption initiates at the edges and mechanical defects in the monolayer. Once the monolayer is covered, the contaminants spread over the additional graphene layers. With this method, we estimate the contamination kinetics. In monolayer graphene, the surface area covered with adsorbed molecules increases with time of air exposure at a rate of 10-14 m2/s, while in bilayer graphene, it is one order of magnitude smaller. Finally, as the contaminants cover the additional graphene layers, friction no longer has a difference concerning the number of graphene layers.

Usefulness of a murine model of hepatic cystic echinococcosis for preclinical drug trials: efficacy of albendazole vs albendazole nanocrystals.

Cystic echinococcosis is a zoonotic infection caused by the larval stage of Echinococcus granulosus sensu lato. The disease is characterized by the long-term growth of cysts, most commonly in the liver and lungs. Although an ideal model of cystic echinococcosis should induce the development of cysts in the liver and imitate the natural infection route, the murine model of intraperitoneal is still widely used in the field of experimental theraphy. The aim of the present work was to evaluate the usefulness of the murine model of hepatic CE for preclinical drug trials. The effectiveness of albendazole could also be assessed by measuring the diameter of the hepatic cyst. The albendazole significantly reduced the size of the cysts. The ultrastructural alterations of the germinal layer of hepatic cysts provoked by albendazole coincided with those observed in the intraperitoneal model. Similar results were obtained with both albendazole doses. Therefore, the efficacy of albendazole nanocrystals in the murine model of hepatic cystic echinococcosis was carried out at albendazole doses of 25 mg/kg. The abdominal ultrasound allows us to assess the response of cysts to drugs only in a qualitative manner. Although the size of cysts in the albendazole nanocrystal group was not significantly lower than that observed with albendazole, at the ultrastructural level, a greater extent of damage was observed. The murine model of hepatic cystic echinococcosis can be effectively used for assessing the effect of novel formulations or compounds. The main advantage of this model is that cysts are located in the orthotopic organ, which resembles the location most commonly found in human cases. In future studies, the usefulness of the model for pharmacokinetics studies in hepatic cysts will be evaluated.

Effectiveness of a two-component nutritional strategy for blood pressure control in individuals with hypertension users of a public health system: a randomized controlled clinical trial.

OBJECTIVE: To evaluate the effectiveness of a nutritional strategy based on two components and adapted for the public health system on blood pressure, cardiometabolic features, self-care, qualify of life and diet quality in individuals with hypertension. METHODS: NUPRESS was an open-label, parallel-group, superiority randomized controlled clinical trial in which participants at least 21 years with hypertension and poorly controlled blood pressure were randomly assigned (1 : 1 allocation ratio) to either an individualized dietary prescription according to nutritional guidelines (control group, n  = 205); or a two-component nutrition strategy, including a goal-directed nutritional counseling and mindfulness techniques (NUPRESS [intervention] group, n  = 205). Primary outcomes were SBP (mmHg) after 24 weeks of follow up and blood pressure control, defined as either having SBP more than 140 mmHg at baseline and achieving 140 mmHg or less after follow-up or having SBP 140 mmHg or less at baseline and reducing the frequency of antihypertensive drugs in use after follow-up. RESULTS: In total, 410 participants were randomized and submitted to an intention-to-treat analysis regarding primary outcomes. Both groups decreased blood pressure, but after adjusting for baseline values, there was no significant difference between them on SBP [intervention-control difference: -0.03 (-3.01; 2.94); P  = 0.98] nor blood pressure control [odds ratio 1.27 (0.82; 1.97); P  = 0.28]. No differences between groups were also detected regarding secondary and tertiary outcomes. CONCLUSION: There was no difference between a two-component nutritional strategy and an established dietary intervention on blood pressure in participants with hypertension.

The Chlamydia trachomatis Inc Tri1 interacts with TRAF7 to displace native TRAF7 interacting partners.

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections in the USA and of preventable blindness worldwide. This obligate intracellular pathogen replicates within a membrane-bound inclusion, but how it acquires nutrients from the host while avoiding detection by the innate immune system is incompletely understood. C. trachomatis accomplishes this in part through the translocation of a unique set of effectors into the inclusion membrane, the inclusion membrane proteins (Incs). Incs are ideally positioned at the host-pathogen interface to reprogram host signaling by redirecting proteins or organelles to the inclusion. Using a combination of co-affinity purification, immunofluorescence confocal imaging, and proteomics, we characterize the interaction between an early-expressed Inc of unknown function, Tri1, and tumor necrosis factor receptor-associated factor 7 (TRAF7). TRAF7 is a multi-domain protein with a RING finger ubiquitin ligase domain and a C-terminal WD40 domain. TRAF7 regulates several innate immune signaling pathways associated with C. trachomatis infection and is mutated in a subset of tumors. We demonstrate that Tri1 and TRAF7 specifically interact during infection and that TRAF7 is recruited to the inclusion. We further show that the predicted coiled-coil domain of Tri1 is necessary to interact with the TRAF7 WD40 domain. Finally, we demonstrate that Tri1 displaces the native TRAF7 binding partners, mitogen-activated protein kinase kinase kinase 2 (MEKK2), and MEKK3. Together, our results suggest that by displacing TRAF7 native binding partners, Tri1 has the capacity to alter TRAF7 signaling during C. trachomatis infection.IMPORTANCEChlamydia trachomatis is the leading cause of bacterial sexually transmitted infections in the USA and preventable blindness worldwide. Although easily treated with antibiotics, the vast majority of infections are asymptomatic and therefore go untreated, leading to infertility and blindness. This obligate intracellular pathogen evades the immune response, which contributes to these outcomes. Here, we characterize the interaction between a C. trachomatis-secreted effector, Tri1, and a host protein involved in innate immune signaling, TRAF7. We identified host proteins that bind to TRAF7 and demonstrated that Tri1 can displace these proteins upon binding to TRAF7. Remarkably, the region of TRAF7 to which these host proteins bind is often mutated in a subset of human tumors. Our work suggests a mechanism by which Tri1 may alter TRAF7 signaling and has implications not only in the pathogenesis of C. trachomatis infections but also in understanding the role of TRAF7 in cancer.

External liquid calibration method for iodide chemical ionization mass spectrometry enables quantification of gas-phase per- and polyfluoroalkyl substances (PFAS) dynamics in indoor air.

Per- and polyfluoroalkyl substances (PFAS) are manufactured chemicals that have been detected across the globe. Fluorotelomer alcohols (FTOHs) are one PFAS class commonly found in indoor air due to emissions from consumer products (e.g., textiles and food packaging) and are human metabolic, atmospheric oxidative, and industrial precursors of perfluoroalkyl carboxylic acids (PFCAs). We developed a quantitative method for real-time analysis of gas-phase FTOHs, perfluoroalkyl acids (PFCAs and GenX), one perfluorooctane sulfonamide (EtFOSA), one fluorotelomer diol (FTdiOH), and one fluorinated ether (E2) using high-resolution time-of-flight chemical ionization mass spectrometry equipped with iodide reagent ion chemistry (I-HR-ToF-CIMS). Herein, we present a direct liquid injection method for external calibration, providing detection limits of 0.19-3.1 pptv for 3 s averaging and 0.02-0.44 pptv for 120 s averaging, with the exception of E2, which had detection limits of 1700 and 220 pptv for 3- and 120 s averaging, respectively. These calibrations enabled real-time gas-phase quantification of 6 : 2 FTOH in room air while microwaving popcorn, with an average peak air concentration of 31.6 ± 4.5 pptv measured 2 meters from a closed microwave. Additionally, 8 : 2 and 10 : 2 FTOH concentrations in indoor air were measured in the presence and absence of a rain jacket, with observed peak concentrations of 110 and 25 pptv, respectively. Our work demonstrates the ability of I-HR-ToF-CIMS to provide real-time air measurements of PFAS relevant to indoor human exposure settings and allow for PFAS source identification. We expect that real-time quantification of other gas-phase PFAS classes is possible, enabling advances in understanding PFAS sources, chemistry, and partitioning.

Evolved histone tail regulates 53BP1 recruitment at damaged chromatin.

The master DNA damage repair histone protein, H2AX, is essential for orchestrating the recruitment of downstream mediator and effector proteins at damaged chromatin. The phosphorylation of H2AX at S139, γH2AX, is well-studied for its DNA repair function. However, the extended C-terminal tail is not characterized. Here, we define the minimal motif on H2AX for the canonical function in activating the MDC1-RNF8-RNF168 phosphorylation-ubiquitination pathway that is important for recruiting repair proteins, such as 53BP1 and BRCA1. Interestingly, H2AX recruits 53BP1 independently from the MDC1-RNF8-RNF168 pathway through its evolved C-terminal linker region with S139 phosphorylation. Mechanistically, 53BP1 recruitment to damaged chromatin is mediated by the interaction between the H2AX C-terminal tail and the 53BP1 Oligomerization-Tudor domains. Moreover, γH2AX-linker mediated 53BP1 recruitment leads to camptothecin resistance in H2AX knockout cells. Overall, our study uncovers an evolved mechanism within the H2AX C-terminal tail for regulating DNA repair proteins at damaged chromatin.

Giant Terahertz Birefringence in an Ultrathin Anisotropic Semimetal.

Manipulating the polarization of light at the nanoscale is key to the development of next-generation optoelectronic devices. This is typically done via waveplates using optically anisotropic crystals, with thicknesses on the order of the wavelength. Here, using a novel ultrafast electron-beam-based technique sensitive to transient near fields at THz frequencies, we observe a giant anisotropy in the linear optical response in the semimetal WTe2 and demonstrate that one can tune the THz polarization using a 50 nm thick film, acting as a broadband wave plate with thickness 3 orders of magnitude smaller than the wavelength. The observed circular deflections of the electron beam are consistent with simulations tracking the trajectory of the electron beam in the near field of the THz pulse. This finding offers a promising approach to enable atomically thin THz polarization control using anisotropic semimetals and defines new approaches for characterizing THz near-field optical response at far-subwavelength length scales.

Cultivating a "Feminine" Surgical Culture: Lessons from Indonesia.

BACKGROUND: Despite a growing number of female physicians, most practicing surgeons in the U.S. are still men. By contrast, Indonesia has achieved notable gender parity among surgeons, with the number of women practicing as plastic surgeons projected to soon surpass men. Achieving more female representation in plastic surgery is important for delivering high-quality care, especially in the face of physician shortages and high burnout. METHODS: This survey study was conducted at the 26th Annual Scientific Meeting of the Indonesian Association of Plastic Reconstructive and Aesthetic Surgeons (InaPRAS) in Manado, Indonesia, during August 2023. Respondents were asked about their perceptions of plastic surgery, mentorship, career motivations, and caregiving responsibilities. Responses were scored using a 3-point Likert scale of agreement to statements (Disagree, Neutral, Agree); χ2 and Fischer's exact test were performed to assess differences in responses by gender. RESULTS: In this validated survey of 175 plastic surgeon trainees and attendings, there were no significant difference between genders in the perception and roles of mentorship in preparing for a career in plastic surgery. Respondents for both genders espoused optimistic views on work-life balance items, including time for family and friends and flexibility of work schedules. CONCLUSION: Indonesia can serve as a model for encouraging greater gender parity in plastic surgery. Community-level interventions such as family leave policies, childcare provisions, and initiatives to promote an inclusive culture will create a more supportive workplace to increase women's representation in plastic surgery in the United States and around the world.

Efficacy of clozapine versus standard treatment in adult individuals with intellectual disability and treatment-resistant psychosis (CLOZAID): study protocol of a multicenter randomized clinical trial.

Background: Intellectual disability (ID) affects approximately 1% of the worldwide population and individuals with ID have a higher comorbidity with mental illness, and specifically psychotic disorders. Unfortunately, among individuals with ID, limited research has been conducted since ID individuals are usually excluded from mental illness epidemiological studies and clinical trials. Here we perform a clinical trial to investigate the effectiveness of clozapine in the treatment of resistant psychosis in individuals with ID. The article highlights the complexity of diagnosing and treating psychopathological alterations associated with ID and advocates for more rigorous research in this field. Methods: A Phase IIB, open-label, randomized, multicenter clinical trial (NCT04529226) is currently ongoing to assess the efficacy of oral clozapine in individuals diagnosed with ID and suffering from treatment-resistant psychosis. We aim to recruit one-hundred and fourteen individuals (N=114) with ID and resistant psychosis, who will be randomized to TAU (treatment as usual) and treatment-with-clozapine conditions. As secondary outcomes, changes in other clinical scales (PANSS and SANS) and the improvement in functionality, assessed through changes in the Euro-QoL-5D-5L were assessed. The main outcome variables will be analyzed using generalized linear mixed models (GLMM), assessing the effects of status variable (TAU vs. Clozapine), time, and the interaction between them. Discussion: The treatment of resistant psychosis among ID individuals must be directed by empirically supported research. CLOZAID clinical trial may provide relevant information about clinical guidelines to optimally treat adults with ID and treatment-resistant psychosis and the benefits and risks of an early use of clozapine in this underrepresented population in clinical trials. Trial registration: Clinicaltrials.gov: NCT04529226. EudraCT: 2020-000091-37.

The Chlamydia effector IncE employs two short linear motifs to reprogram host vesicle trafficking.

Chlamydia trachomatis, a leading cause of bacteria sexually transmitted infections, creates a specialized intracellular replicative niche by translocation and insertion of a diverse array of effectors (Incs) into the inclusion membrane. Here, we characterize IncE, a multi-functional Inc that encodes two non-overlapping short linear motifs (SLiMs) within its short cytosolic C-terminus. The proximal SLiM mimics an R-SNARE motif to recruit syntaxin (STX) 7 and 12-containing vesicles to the inclusion. The distal SLiM mimics the Sorting Nexin (SNX) 5 and 6 cargo binding site to recruit SNX6-containing vesicles to the inclusion. By simultaneously binding to two distinct vesicle classes, IncE reprograms host cell trafficking to promote the formation of a class of hybrid vesicles at the inclusion that are required for C. trachomatis intracellular development. Our work suggests that Incs may have evolved SLiMs to facilitate rapid evolution in a limited protein space to disrupt host cell processes.

Development, Validation, and Comparison of a Novel Nociception/Anti-Nociception Monitor against Two Commercial Monitors in General Anesthesia.

In this paper, we present the development and the validation of a novel index of nociception/anti-nociception (N/AN) based on skin impedance measurement in time and frequency domain with our prototype AnspecPro device. The primary objective of the study was to compare the Anspec-PRO device with two other commercial devices (Medasense, Medstorm). This comparison was designed to be conducted under the same conditions for the three devices. This was carried out during total intravenous anesthesia (TIVA) by investigating its outcomes related to noxious stimulus. In a carefully designed clinical protocol during general anesthesia from induction until emergence, we extract data for estimating individualized causal dynamic models between drug infusion and their monitored effect variables. Specifically, these are Propofol hypnotic drug to Bispectral index of hypnosis level and Remifentanil opioid drug to each of the three aforementioned devices. When compared, statistical analysis of the regions before and during the standardized stimulus shows consistent difference between regions for all devices and for all indices. These results suggest that the proposed methodology for data extraction and processing for AnspecPro delivers the same information as the two commercial devices.

Arterial Stiffness Changes in Adult Cancer Patients Receiving Anticancer Chemotherapy: A Real-World Bicentric Experience.

Background Chemotherapy correlates to acute and long-term cardiotoxicity, is reflected clinically by myocardial and vascular endothelial dysfunction, and can cause cardiovascular complications. Thus, early diagnosis of cardiovascular disease in cancer patients undergoing anti-cancer treatment is necessary to enhance long-term survival. Our principal objective in this study was to discern the impact of specific anti-cancer chemotherapeutics and biologics on arterial stiffness alterations before and after the administration. Methods Conducted at Mustafa Bacha University Hospital, Algeria, the study focused on arterial stiffness in anti-cancer chemotherapy patients. Assessments included blood pressure, diabetes, and dyslipidemia, with precise measurements using validated systems, particularly pulse wave velocity (PWV). Various chemotherapy protocols were applied, and statistical analysis with R software (R Foundation for Statistical Computing, Vienna, Austria) maintained a significance level of p=0.05. Key outcomes centered on carotid-femoral PWV and secondary endpoints such as central and peripheral pressures and pulse pressure (PP). Univariate and bivariate analyses were conducted using appropriate statistical tests.  Results A comparative prospective observational study was completed on 58 patients (34 women and 24 men; mean age: 52.64 +/- 12.12 years) treated with anti-cancer chemotherapy agents. Our evaluation included a complete clinical exam, electrocardiogram, Doppler echocardiography, and applanation tonometry with arterial stiffness measurement using PWV. Patients presented significantly higher levels of carotid-femoral PWV, regardless of the chosen chemotherapy protocol, with no return to the initial level after one year of stopping treatment (p-value < 0.01). Moreover, this increase was more significant in patients with diabetes and hypertension and patients treated with monoclonal antibodies or intercalants.  Conclusion This prospective study shows that chemotherapy patients have elevated arterial stiffness, emphasizing the need to assess PWV and monitor cardiovascular risk factors. PP measurement with PWV could improve risk management.

Redox Regulation of LAT Enhances T Cell-Mediated Inflammation.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data show that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

Storylines of family medicine VII: family medicine across the lifespan.

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'VII: family medicine across the lifespan', authors address the following themes: 'Family medicine maternity care', 'Seeing children as patients brings joy to work', 'Family medicine and the care of adolescents', 'Reproductive healthcare across the lifespan', 'Men's health', 'Care of older adults', and 'Being with dying'. May readers appreciate the range of family medicine in these essays.

The Chlamydia trachomatis Inc Tri1 interacts with TRAF7 to displace native TRAF7 interacting partners.

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections in the US and of preventable blindness worldwide. This obligate intracellular pathogen replicates within a membrane-bound inclusion, but how it acquires nutrients from the host while avoiding detection by the innate immune system is incompletely understood. C. trachomatis accomplishes this in part through the translocation of a unique set of effectors into the inclusion membrane, the inc lusion membrane proteins (Incs). Incs are ideally positioned at the host-pathogen interface to reprogram host signaling by redirecting proteins or organelles to the inclusion. Using a combination of co-affinity purification, immunofluorescence confocal imaging, and proteomics, we characterize the interaction between an early-expressed Inc of unknown function, Tri1, and tumor necrosis factor receptor associated factor 7 (TRAF7). TRAF7 is a multi-domain protein with a RING finger ubiquitin ligase domain and a C-terminal WD40 domain. TRAF7 regulates several innate immune signaling pathways associated with C. trachomatis infection and is mutated in a subset of tumors. We demonstrate that Tri1 and TRAF7 specifically interact during infection and that TRAF7 is recruited to the inclusion. We further show that the predicted coiled-coil domain of Tri1 is necessary to interact with the TRAF7 WD40 domain. Finally, we demonstrate that Tri1 displaces the native TRAF7 binding partners, mitogen activated protein kinase kinase kinase 2 (MEKK2) and MEKK3. Together, our results suggest that by displacing TRAF7 native binding partners, Tri1 has the capacity to alter TRAF7 signaling during C. trachomatis infection. Importance: Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections in the US and preventable blindness worldwide. Although easily treated with antibiotics, the vast majority of infections are asymptomatic and therefore go untreated, leading to infertility and blindness. This obligate intracellular pathogen evades the immune response, which contributes to these outcomes. Here, we characterize the interaction between a C. trachomatis secreted effector, Tri1, and a host protein involved in innate immune signaling, TRAF7. We identified host proteins that bind to TRAF7 and demonstrate that Tri1 can displace these proteins upon binding to TRAF7. Remarkably, the region of TRAF7 to which these host proteins bind is often mutated in a subset of human tumors. Our work suggests a mechanism by which Tri1 may alter TRAF7 signaling and has implications not only in the pathogenesis of C. trachomatis infections, but also in understanding the role of TRAF7 in cancer.

Ectopic Expression of Neurod1 Is Sufficient for Functional Recovery following a Sensory-Motor Cortical Stroke.

Stroke is the leading cause of adult disability worldwide. The majority of stroke survivors are left with devastating functional impairments for which few treatment options exist. Recently, a number of studies have used ectopic expression of transcription factors that direct neuronal cell fate with the intention of converting astrocytes to neurons in various models of brain injury and disease. While there have been reports that question whether astrocyte-to-neuron conversion occurs in vivo, here, we have asked if ectopic expression of the transcription factor Neurod1 is sufficient to promote improved functional outcomes when delivered in the subacute phase following endothelin-1-induced sensory-motor cortex stroke. We used an adeno-associated virus to deliver Neurod1 from the short GFAP promoter and demonstrated improved functional outcomes as early as 28 days post-stroke and persisting to at least 63 days post-stroke. Using Cre-based cell fate tracking, we showed that functional recovery correlated with the expression of neuronal markers in transduced cells by 28 days post-stroke. By 63 days post-stroke, the reporter-expressing cells comprised ~20% of all the neurons in the perilesional cortex and expressed markers of cortical neuron subtypes. Overall, our findings indicate that ectopic expression of Neurod1 in the stroke-injured brain is sufficient to enhance neural repair.

Factors Associated with the Prevalence of Salmonella, Generic Escherichia coli, and Coliforms in Florida's Agricultural Soils.

Limited data exist on the environmental factors that impact pathogen prevalence in the soil. The prevalence of foodborne pathogens, Salmonella and Listeria monocytogenes, and the prevalence and concentration of generic E. coli in Florida's agricultural soils were evaluated to understand the potential risk of microbial contamination at the preharvest level. For all organisms but L. monocytogenes, a longitudinal field study was performed in three geographically distributed agricultural areas across Florida. At each location, 20 unique 5 by 5 m field sampling sites were selected, and soil was collected and evaluated for Salmonella presence (25 g) and E. coli and coliform concentrations (5 g). Complementary data collected from October 2021 to April 2022 included: weather; adjacent land use; soil properties, including macro- and micro-nutrients; and field management practices. The overall Salmonella and generic E. coli prevalence was 0.418% (1/239) and 11.3% (27/239), respectively; with mean E. coli concentrations in positive samples of 1.56 log CFU/g. Farm A had the highest prevalence of generic E. coli, 22.8% (18/79); followed by Farm B, 10% (8/80); and Farm C 1.25% (1/80). A significant relationship (p < 0.05) was observed between generic E. coli and coliforms, and farm and sampling trip. Variation in the prevalence of generic E. coli and changes in coliform concentrations between farms suggest environmental factors (e.g. soil properties) at the three farms were different. While Salmonella was only detected once, generic E. coli was detected in Florida soils throughout the duration of the growing season meaning activities that limit contact between soil and horticultural crops should continue to be emphasized. Samples collected during an independent sampling trip were evaluated for L. monocytogenes, which was not detected. The influence of local environmental factors on the prevalence of indicator organisms in the soil presents a unique challenge when evaluating the applicability of more global models to predict pathogen prevalence in preharvest produce environments.

Rare SNP in the HELB gene interferes with RPA interaction and cellular function of HELB.

HELB is a human helicase involved in initiation of DNA replication, the replication stress response, and regulation of double-strand DNA break repair. rs75770066 is a rare SNP in the HELB gene that affects age at natural menopause. rs75770066 results in a D506G substitution in an acidic patch within the 1A domain of the helicase that is known to interact with RPA. We found that this amino acid change dramatically impairs the cellular function of HELB. D506G-HELB exhibits impaired interaction with RPA, which likely results in the effects of rs75770066 as this reduces recruitment of HELB to sites of DNA damage. Reduced recruitment of D506G-HELB to double-strand DNA breaks and the concomitant increase in homologous recombination likely alters the levels of meiotic recombination, which affects the viability of gametes. Because menopause occurs when oocyte levels drop below a minimum threshold, altered repair of meiotic double-stranded DNA breaks has the potential to directly affect the age at natural menopause.