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781 result(s) for "Jones, Jesse"
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Structural basis for peroxidase encapsulation inside the encapsulin from the Gram-negative pathogen Klebsiella pneumoniae
Encapsulins are self-assembling protein nanocompartments capable of selectively encapsulating dedicated cargo proteins, including enzymes involved in iron storage, sulfur metabolism, and stress resistance. They represent a unique compartmentalization strategy used by many pathogens to facilitate specialized metabolic capabilities. Encapsulation is mediated by specific cargo protein motifs known as targeting peptides (TPs), though the structural basis for encapsulation of the largest encapsulin cargo class, dye-decolorizing peroxidases (DyPs), is currently unknown. Here, we characterize a DyP-containing encapsulin from the enterobacterial pathogen Klebsiella pneumoniae . By combining cryo-electron microscopy with TP and TP-binding site mutagenesis, we elucidate the molecular basis for cargo encapsulation. TP binding is mediated by cooperative hydrophobic and ionic interactions as well as shape complementarity. Our results expand the molecular understanding of enzyme encapsulation inside protein nanocompartments and lay the foundation for rationally modulating encapsulin cargo loading for biomedical and biotechnological applications. Peroxidase encapsulins are self-assembling protein compartments involved in oxidative stress response found in many pathogens. Here, the authors characterize the structural basis of peroxidase encapsulation inside the Klebsiella pneumoniae encapsulin.
Sleep drive is coupled to tissue damage via shedding of Caenorhabditis elegans EGFR ligand SISS-1
The benefits of sleep extend beyond the nervous system. Peripheral tissues impact sleep regulation, and increased sleep is observed in response to damaging conditions, even those that selectively affect non-neuronal cells. However, the ‘sleep need’ signal released by stressed tissues is not known. Sleep in the nematode C. elegans is independent of circadian cues and can be triggered rapidly by damaging conditions. This stress-induced sleep is mediated by neurons that require the Epidermal Growth Factor Receptor (EGFR) for their sleep-promoting function, but the only known C. elegans EGFR ligand, LIN-3, is not required for sleep. Here we describe SISS-1 ( s tress- i nduced s leeples s ), an EGF family ligand that is required for stress-induced sleep. We show that SISS-1 overexpression induces sleep in an EGFR-dependent, sleep neuron-dependent manner. We find that SISS-1 undergoes stress-responsive shedding by the ADM-4/ADAM17 metalloprotease, and that the ADM-4 site of action depends on the tissue specificity of the stressor. Our findings support a model in which SISS-1 is released from damaged tissues to activate EGFR in sleep neurons, identifying a molecular link between cellular stress and organismal sleep drive. Our data also point to a mechanism insulating this sleep signal from EGFR-mediated signaling during development. Cellular damage promotes sleep in C. elegans via Epidermal Growth Factor Receptors in sleep-promoting neurons, but the ligand was unknown. Here, the authors identify an EGFR ligand that is shed from damaged tissues by the protease ADM-4/ADAM17 to promote sleep.
Characteristics and outcomes of pediatric dural arteriovenous fistulas: a systematic review
Background Dural arteriovenous fistulas (dAVF) are arteriovenous shunts in communication with the dural vasculature in the brain or spine. Apart from single-center series, risk factors and treatment outcomes for pediatric dAVFs are largely undescribed. Methods We performed a systematic literature review of pediatric (< 18 years at diagnosis) intracranial and spinal dAVF according to PRISMA guidelines. We queried PubMed, CINAHL, SCOPUS, and Embase databases without time/date restriction. Search strings included a variety of MeSH keywords relating to dural AV fistulas in combination with MeSH keywords related to pediatric cases (see Appendix ). Manuscripts describing patients diagnosed with dural sinus malformations or pial AVF were excluded. Results We identified 61 studies describing 69 individual patients. Overall, dAVF were more common in males (55.1%) with a mean age of diagnosis (5.17 ± 4.42 years). Approximately 20.2% of patients presented with cardiovascular disease (CVD), and 31.9% were discovered incidentally on neuroimaging studies. Transverse-sigmoid junction was the most common location (17.3%). Ninety-three percent (64 patients) were treated, most commonly using endovascular embolization (68.1%) followed by surgery (8.7%) and radiosurgery (2.9%). Almost half (43.8%) of dAVFs were completely obliterated. Of the 64 procedures, there were 19 neurological complications (29.7%) of varying severity where 12.5% were considered transient (i.e., pseudomeningocele) and 17.2% permanent (i.e., mortality secondary to acute sinus thrombosis, etc.). Conclusion There is a paucity of information on pediatric dAVFs. This systematic review summarizes the published cases of dAVFs in the pediatric population. While the rate of missing data is high, there is publication bias, and precise details regarding complications are difficult to ascertain, this review serves as a descriptive summary of pediatric dAVFs.
Nanoparticulate Copper Cluster-Mediated Biosensing of Cardiac Biomolecular Markers
Being a leading cause of death, heart diseases across the globe need special attention to enable early diagnosis. Metal nanoparticle-mediated biosensors are useful clinical tools for the early detection of bio-analytes. The size-dependent surface plasmon resonance (SPR) of metal nanoparticles can be effectively utilized for the same purpose. The early detection of heart diseases can be evaluated by monitoring the troponin level. A copper nanoparticle-mediated troponin biosensor was developed through antibody conjugation for troponin I and troponin T. The copper nanosensor shows a concentration-dependent SPR change towards troponin T and troponin I.
Stereotactic radiosurgery treatment of pediatric arteriovenous malformations: a PRISMA systematic review and meta-analysis
Background Stereotactic radiosurgery (SRS) is considered a safe definitive treatment for pediatric arteriovenous malformations (AVMs) upon indicated presentations. There are no published guidelines by the International Stereotactic Radiosurgery Society (ISRS) detailed with indications or characteristics that warrant SRS, other than the guideline that SRS is a safe and efficacious treatment for pediatric AVMs. SRS is performed using either Gamma Knife (GK) or Linear Accelerator (LINAC). This systematic review aims to uncover treatment, differences in GK and LINAC outcomes, and AVM characteristics that lead to high obliteration rates and suggest future studies to determine treatment decisions, raise obliteration rates, and lower complication rates in SRS treatment of pediatric AVMs. Methods We performed a systematic review according to PRISMA guidelines across PubMed, Embase, and SCOPUS utilizing search terms related to pediatric patients, AVMS, and SRS. We collected data from the 32 full-text studies and 4 abstracts that met inclusion criteria. Subsequent pooled analysis was performed on GK vs LINAC obliteration rates, followed by sub-cohort analysis of all SRS patients with hemorrhagic presentation, Spetzler-Martin (SM) Grade, and prior procedure and their effect on obliteration rates. Results The 36 studies reported 3425 patients, with a slight male preponderance (1662 patients, 48.5%). The obliteration analysis included 2834 patients that met follow-up criteria and contained obliteration data. The weighted mean age was 12.63 years. Pooled cohort analysis found no significant difference in obliteration proportions when comparing GK to LINAC ( P  = 0.7449), with an overall obliteration rate of 63% in patients with at least 1 year follow-up. The sub-cohort analysis of all patients treated with SRS revealed that presentation with AVM hemorrhage was associated with increased obliteration (CE: RR = 1.22 [95%CI = 1.09–1.35; RE: RR = 1.22, 95%CI = 10.6–1.40; prediction interval = 1.07–1.38) with low heterogeneity ( I 2  = 17.1%, τ 2  < 0.0001, p  = 0.2902). Smaller SM grade was not statistically associated with increased obliteration (CE: RR = 1.25 [95%CI = 0.87–1.81]; RE: RR = 1.84 [95%CI = 0.97–3.50]; prediction interval = 0.38–8.86) and moderate levels of heterogeneity were detected ( I 2  = 45.2%, τ 2  = 0.2668, p  = 0.1042). Procedure prior to SRS also had higher obliteration rates than no prior procedure (CE: RR = 0.77 [95%CI = 0.61–0.86]; RE: RR = 0.71 [95%CI = 0.54–0.92]; prediction interval = 0.36–1.39) with low to moderate heterogeneity ( I 2  = 27.6%, τ 2  = 0.0.0264, p  = 0.2466). Conclusion SRS is a safe and effective treatment for pediatric AVMs. This study suggests that there are no differences in obliteration between GK and LINAC, with increased obliteration in patients with hemorrhage at presentation and procedures prior to SRS treatment. Further multicenter, prospective studies are necessary to dictate future treatment decisions.
Pediatric non-galenic pial arteriovenous fistula’s characteristics and outcomes: a systematic review
Introduction Pediatric non-galenic pial arteriovenous fistulas (pAVFs) are rare vascular malformations that are characterized by a pial arterial-venous connection without an intervening capillary bed. Outcomes and treatment strategies for pAVFs are highly individualized, owing to the rarity of the disease and lack of large-scale data guiding optimal treatment approaches. Methods We performed a systematic review of pediatric patients (< 18 years at diagnosis) diagnosed with a pAVF by digital subtraction angiogram (DSA). The demographics, treatment modalities, and outcomes were documented for each patient and clinical outcome data was collected. Descriptive information stratified by outcome scores were classified as follows: 1 = excellent (no deficit and full premorbid activity), 2 = good (mild deficit and full premorbid activity), 3 = fair (moderate deficit and impaired activity), 4 = poor (severe deficit and dependent on others), 5 = death. Results A total of 87 studies involving 231 patients were identified. Median age at diagnosis was 3 years (neonates to 18 years). There was slight male preponderance (55.4%), and 150 subjects (81.1%*) experienced excellent outcomes after treatment. Of the 189 patients treated using endovascular approaches, 80.3% experienced excellent outcomes and of the 15 patients surgically treated subjects 75% had an excellent outcome. The highest rate of excellent outcomes was achieved in patients treated with Onyx (95.2%) and other forms of EvOH (100%). High output heart failure and comorbid vascular lesions tended to result in worse outcomes, with only 54.2% and 68% of subjects experiencing an excellent outcome, respectively. *Outcomes were reported in only 185 patients. Conclusion pAVFs are rare lesions, necessitating aggregation of patient data to inform natural history and optimal treatment strategies. This review summarizes the current literature on pAVF in children, where children presenting with heart failure as a result of high flow through the lesion were less likely to experience an excellent outcome. Prospective, large-scale studies would further characterize pediatric pAVFs and enable quantitative analysis of outcomes to inform best treatment practices.
Stable Inheritance of Transgene and Yellow Fluorescent Protein Gene Expression in Progeny of Transgenic Cacao (Theobroma cacao) Plants
Genetic engineering tools have the potential to rapidly and precisely improve the genome of slow-to-breed cacao. We previously developed an efficient protocol for transforming cacao using cotyledonary explants derived from secondary somatic embryos via Agrobacterium tumefaciens. In this study, we demonstrate that our transformation protocol is successful in elite cultivars, INIAPG-038 and Matina 1-6, producing fertile seeds with stable visual marker inheritance regardless of whether the transgenic plants were used as the pollen or ovule donor. Three vectors were used in the transformations, each containing genes for enhanced yellow fluorescent protein (eyfp) and neomycin phosphotransferase II (nptII). Three transgenic INIAPG-038 events and one transgenic Matina 1-6 event were used to evaluate seed fertility and the stability of transgene inheritance in cacao seeds and plants. The T1 progeny of these four transgenic events were analyzed for YFP expression and transgene presence. YFP expression segregated at a 1:1 ratio in all events when the transgenic plants were crossed with non-transgenic plants, while a 3:1 segregation was observed when transgenic events were crossed with each other. The transgenic plants exhibited a normal phenotype compared to non-transgenic control plants, producing seeds with a 97% germination rate.
Perceived health risk associated with washroom cleaning among sanitation workers in a public tertiary institution in Ghana
The advantages of better sanitation and proper hygienic practices are widely acknowledged and practised as a successful approach to infectious disease control. However, organizational inefficiencies and structural challenges hinder better sanitation services and more importantly neglect of the well-being or health of sanitation workers. This study examines the perceived health risk associated with washroom cleaning among sanitation workers in a public tertiary institution in Ghana. The study employed the hermeneutic phenomenological design with a qualitative approach. The study found that sanitation workers used strong disinfectants and cleaning chemicals in cleaning the washrooms. The study revealed that sanitation workers faced stigma and discrimination, low remuneration and job insecurity and inadequate personal protective equipment. It was also found that sanitation workers experienced musculoskeletal, respiratory, and psychosocial health risks. The findings imply that sanitation workers face a challenging and high-risk work environment, with significant health risk, inadequate protection, and limited support. The study underscores the need for improved working conditions, proper safety equipment, fair remuneration and interventions to address both physical and psychosocial health risks.
Livelihood resilience among street hawkers during Covid-19 lockdown in the Awutu Senya East Municipality, Ghana
PurposeThe study assesses the livelihood resilience strategies among street hawkers during COVID-19 lockdown in the Awutu Senya East Municipality in Ghana.Design/methodology/approachUsing the explanatory case study approach, 12 participants (hawkers) were sampled with the aid of the purposive and convenience sampling techniques. An interview guide was used to collect data.FindingsThe study found that street hawking business, prior to the COVID-19 lockdown was a lucrative venture. The COVID-19 lockdown however had mental, psychological and economic effects on the street hawkers in ASEM causing stress, anxiety. loneliness, loss of business capital, and loss of jobs. Hawkers nevertheless demonstrated resilience in their psychological well-being by adopting strategies such as patronizing digital/social media platforms for funny content and entertainment. Hawkers also showed economic resilience through selling products on digital/social media platforms, relied on personal savings, received social support from family members and religious bodies. Government policies and interventions in the form of free water and electricity played a crucial role in building resilience of street hawkers during the COVID-19 lockdown.Practical implicationsThe study shows that hawking is a vital avenue for entrepreneurial engagement reducing barriers to entry in formal trading, hence should be considered as key economic venture in the country’s economy. Again, the findings of the study deepen the understanding of stakeholders on the effects of COVID-19 on the psychological and economic life of street hawkers and offers insights into managing both psychosocial and financial stress during crises, emphasizing the potential benefits of resilient strategies for more effective crisis management. The study findings provide insights for government and policymakers on the experiences and coping mechanisms of the vulnerable groups and communities, particularly hawkers during the pandemic.Originality/valueThe study qualitatively assesses the psychological and economic effects of the COVID-19 lockdown and the livelihood resilience strategies employed by street hawkers during the COVID-19 lockdown in ASEM, Ghana.
Ultrasmall Superparamagnetic Iron Oxide Nanoparticles as Positive Contrast Agents in Low‐Field Magnetic Resonance Imaging
Ultrasmall superparamagnetic iron oxide nanoparticles (usSPIONs) are promising alternatives to gadolinium‐based contrast agents for positive contrast enhancement in magnetic resonance imaging (MRI). Unlike larger SPIONs that primarily function as T2/T2* negative contrast agents, usSPIONs with core diameters below 5 nm can effectively shorten T1 relaxation times, producing bright signals in T1‐weighted images. This distinct behavior stems from their unique magnetic properties, including single‐domain configurations, surface spin canting, and rapid Néel relaxation dynamics, which are particularly enhanced at low magnetic field strengths. The biocompatibility of iron oxide, efficient renal clearance pathways, and versatility for surface functionalization offer potential advantages over gadolinium‐based agents, especially regarding safety concerns related to nephrogenic systemic fibrosis and gadolinium deposition. These nanoparticles show particular promise for applications in low‐field MRI, vascular imaging, targeted molecular imaging, and theranostic platforms. Although challenges remain in optimizing synthesis methods for consistent production of monodisperse usSPIONs with tailored surface chemistry, ongoing research continues to advance their potential for clinical translation. This review explores the mechanisms, synthesis approaches, applications, and future perspectives of usSPIONs as positive contrast agents in MRI. Ultrasmall superparamagnetic iron oxide nanoparticles emerge as promising positive contrast agents for low‐field MRI. Unlike larger SPIONs, these particles exhibit enhanced T1 relaxivity through rapid magnetic fluctuations and surface spin canting. Their biocompatibility, renal clearance pathway, and bright contrast generation offer safer alternatives to gadolinium‐based agents, opening new possibilities for targeted imaging, angiography, and point‐of‐care diagnostics. Based on our discussion in the manuscript and current understanding of size‐dependent magnetic properties, we propose the following standardized nomenclature recommendations: (1) “paramagnetic‐like usSPIONs” for particles < 5 nm exhibiting predominantly T1 contrast effects with minimal superparamagnetic behavior; (2) “surface‐modified superparamagnetic nanoparticles” for particles 5–10 nm where surface effects significantly alter classical superparamagnetic behavior; and (3) “classical superparamagnetic iron oxide nanoparticles” for particles > 10 nm exhibiting traditional superparamagnetic behavior with dominant T2/T2* effects.