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Intervertebral disc degeneration is rescued by TGFβ/BMP signaling modulation in an ex vivo flamin B mouse model

Bone Research 2022年第3期10卷 524-535页

作者： jennifer zieba Kimberly N.Forlenza Kelly Heard Jorge H.Martin Michaela Bosakova Daniel H.Cohn Stephen P.Robertson Pavel Krejci Deborah Krakow Department of Orthopedic Surgery Los AngelesCA 90095USA Department of Biology Faculty of MedicineMasaryk University62500 BrnoCzech Republic International Clinical Research Center St.Anne’s University Hospital65691 BrnoCzech Republic Institute of Animal Physiology and Genetics Czech Academy of Sciences60200 BrnoCzech Republic Department of Molecular Cell and Developmental Biology University of CaliforniaLos AngelesLos AngelesCA 90095USA Department of Women’s and Children’s Health Dunedin School of MedicineUniversity of OtagoDunedinNew Zealand Department of Human Genetics Los AngelesCA 90095USA Department of Obstetrics and Gynecology Los AngelesCA 90095USA Department of Pediatrics David Geffen School of Medicine at University of CaliforniaLos AngelesLos AngelesCA 90095USA

Spondylocarpotarsal syndrome(SCT) is a rare musculoskeletal disorder characterized by short stature and vertebral, carpal, and tarsal fusions resulting from biallelic nonsense mutations in the gene encoding filamin B(FLNB). Utilizing a FLNB knockout mouse,we showed that the vertebral fusions in SCT evolved from intervertebral disc(IVD) degeneration and ossification of the annulus fibrosus(AF), eventually leading to full trabecular bone formation. This resulted from alterations in the TGFβ/BMP signaling pathway that included increased canonical TGFβ and noncanonical BMP signaling. In this study, the role of FLNB in the TGFβ/BMP pathway was elucidated using in vitro, in vivo, and ex vivo treatment methodologies. The data demonstrated that FLNB interacts with inhibitory Smads 6 and 7(i-Smads) to regulate TGFβ/BMP signaling and that loss of FLNB produces increased TGFβ receptor activity and decreased Smad 1 ubiquitination. Through the use of small molecule inhibitors in an ex vivo spine model, TGFβ/BMP signaling was modulated to design a targeted treatment for SCT and disc degeneration. Inhibition of canonical and noncanonical TGFβ/BMP pathway activity restored Flnb-/-IVD morphology. These most effective improvements resulted from specific inhibition of TGFβand p38 signaling activation. FLNB acts as a bridge for TGFβ/BMP signaling crosstalk through i-Smads and is key for the critical balance in TGFβ/BMP signaling that maintains the IVD. These findings further our understanding of IVD biology and reveal new molecular targets for disc degeneration as well as congenital vertebral fusion disorders.

关键词： TGFβ vivo BMP treatment

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Working toward an integrated plasticity/network framework for repetitive transcranial magnetic stimulation to inform tailored treatments

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Neural Regeneration Research 2024年第7期19卷 1423-1424页

作者： Jessica Moretti jennifer Rodger Experimental and Regenerative Neurosciences School of Biological SciencesUniversity of Western AustraliaCrawleyWAAustralia Brain Plasticity Lab Perron Institute for Neurological and Translational ScienceNedlandsWAAustralia

Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying *** rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.

关键词： stimulation transcranial treatment

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Implications of regional identity for neural stem and progenitor cell transplantation in the injured or diseased nervous system

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Neural Regeneration Research 2024年第4期19卷 715-716页

作者： Prakruthi Amar Kumar jennifer N.Dulin Department of Biology Texas A&M UniversityCollege Station Texas A&M Institute for Neuroscience Texas A&M UniversityCollege Station

Neural stem and progenitor cell(NSPC)transpla ntation has emerged as a promising therapeutic strategy for replacing lost neuronal populations and repairing damaged neural circuits following nervous system injury and disease.A great deal of experimental work has investigated the biology of NSPC grafting in preclinical animal models;more recently.

关键词： neural system injured

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Classifying moisture sources associated with snowfall in the mountains of Lesotho

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Journal of Mountain Science 2024年第6期21卷 1941-1953页

作者： Alexi M.MARINAKI jennifer M.FITCHETT School of Geography Archaeology and Environmental StudiesUniversity of the WitwatersrandPrivate Bag X3Wits 2050South Africa

An average of eight snowfall events occur each year in the eastern Lesotho *** snowfall events are typically associated with cut-off low(CoLs)systems and mid-latitude ***,the moisture sources of the snowfall are unclassified and *** Hybrid Single-Particle Lagrangian Integrated Trajectory(HYSPLIT)model,an air mass back trajectory model,has been used to evaluate moisture source waters locally in southern Africa and internationally in China and *** study uses HYSPLIT to determine the source moisture of snow in Lesotho.A list of all 82 snowfall events in Lesotho spanning 2017 to 2022 was compiled using the Snow Report SA Instagram page,including the date and location of snowfall.A 72-hour back trajectory for each snowfall event was initiated for both Afriski and the whole of *** amounts to models of moisture source trajectories for 28 and 82 snowfall days,*** air mass pathways are classified according to their frequency per snowfall event,per month in the snow season,per year and for the full *** this,associated moisture source regions and dominant air mass trajectories were *** study reports that the air mass trajectories associated with Afriski and Lesotho as a whole are very *** most common pathway of air mass trajectories transporting snow-bearing moisture to Lesotho was an inland trajectory from the northern regions of southern *** pathway makes up 16.6%of all trajectories reported and is associated with the Angola Low,the Congo Air Boundary and the *** High Pressure.

关键词： Eastern Lesotho Highlands Afriski Snow Cut-off Lows HYSPLIT Synoptic Climatology

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Increasing polymer scission rate by tying an overhand knot

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Science China Chemistry 2024年第11期67卷 3498-3499页

作者： Yuheng Hu jennifer T.Ou Jim Y.Huang Yuanning Feng Department of Chemistry and Biochemistry The University of Oklahoma

Similar to the phenomenon of knotted ropes in life, knotted climbing ropes will reduce their strength due to knots. Although computer simulations [1], theoretical speculation[2,3], and intuition [3] suggest that similar processes may occur at the nanoscale, this hypothesis has not been experimentally proven before. With the increasing maturity of molecular recognition and self-assembly, a research communication by Leigh et al. [4] published in Nature Chemistry introduced a molecular overhand knot into a polymer to study its effect on the scission rate of the polymer chain under tension.

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Exercise and exerkine upregulation:Brain-derived neurotrophic factor as a potential non-pharmacological therapeutic strategy for Parkinson’s disease

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BIOCELL 2024年第5期48卷 693-706页

作者： VIRAAJ VISHNU PRASAD jennifer SALLY SAMSON VENKATACHALAM DEEPA PARVATHI Department of Biomedical Sciences Sri Ramachandra Institute of Higher Education and ResearchChennai600116India

Physical activity and exercise have several beneficial roles in enhancing both physiological and psychological well-being of an *** addition to aiding the regulation of aerobic and anaerobic metabolism,exercise can stimulate the synthesis of exerkine hormones in the circulatory *** several exerkines that have been investigated for their therapeutic potential,Brain-derived neurotrophic factor(BDNF)is considered the most promising candidate,especially in the management of neurodegenerative *** to the ability of physical activity to enhance BDNF synthesis,several experimental studies conducted so far have validated this hypothesis and produced satisfactory results at the pre-clinical *** review highlights some of the recent animal model studies that have evaluated the efficiency of exercise in enhancing BDNF synthesis and promoting neuroprotective ***,this review focuses on understanding the therapeutic benefits of exercise-induced exerkine synthesis as a non-pharmacological strategy in Parkinson’s disease(PD).Regarding physical activity and exerkine induction,the neuromuscular electrical stimulation(NMES)strategy could be considered as an alternate treatment modality for patients affected with PD.

关键词： Exercise therapy Dopaminergic neurons Parkinson’s disease Brain-derived neurotrophic factor Electrical stimulation

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A predictive model for ethylene-mediated auxin and cytokinin patterning in the Arabidopsis root

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Plant Communications 2024年第7期5卷 120-137页

作者： Simon Moore George Jervis jennifer F.Topping Chunli Chen Junli Liu Keith Lindsey Department of Biosciences Durham UniversitySouth RoadDurham DH13LEUK Hubei Hongshan Laboratory College of Life Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China National Key Laboratory for Germplasm Innovation and Utilization for Fruit and Vegetable Horticultural Crops Huazhong Agricultural UniversityWuhanHubei 430070China

The interaction between auxin and cytokinin is important in many aspects of plant *** measurements of both auxin and cytokinin concentration and reporter gene expression clearly show the coexistence of auxin and cytokinin concentration patterning in Arabidopsis root ***,in the context of crosstalk among auxin,cytokinin,and ethylene,little is known about how auxin and cytokinin concentration patterns simultaneously emerge and how they regulate each other in the Arabidopsis *** work utilizes a wide range of experimental observations to propose a mechanism for simultaneous patterning of auxin and cytokinin *** addition to revealing the regulatory relationships between auxin and cytokinin,this mechanism shows that ethylene signaling is an important factor in achieving simultaneous auxin and cytokinin patterning,while also predicting other experimental *** the mechanism with a realistic in silico root model reproduces experimental observations of both auxin and cytokinin *** made by the mechanism can be compared with a variety of experimental observations,including those obtained by our group and other independent experiments reported by other *** of these predictions include patterning of auxin biosynthesis rate,changes in PIN1 and PIN2 patterns in pin3,4,7 mutants,changes in cytokinin patterning in the pls mutant,PLS patterning,and various trends in different *** research reveals a plausible mechanism for simultaneous patterning of auxin and cytokinin concentrations in Arabidopsis root development and suggests a key role for ethylene pattern integration.

关键词： Arabidopsis root auxin patterning cytokinin patterning ethylene signaling in silico digital root spatiotemporal modeling

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Germline Gene-Editing Creates Enhanced Livestock-Technical and Especially Ethical Issues Challenge Its Use in Humans

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Engineering 2024年第2期33卷 3-5页

作者： jennifer Welsh Senior Technology Writer

Using clustered regularly interspaced short palindromic repeats(CRISPR)-based molecular tools,scientists are engineering-as they are also doing with plants.-animals with advantageous traits,like disease resistance and improved food *** these innovative techniques could one day be applied in humans,technical hurdles and ethical concerns likely place this possibility far in the future,The enhancements rely on germline gene editing,which alters the genes in a way that passes the changes on to *** m-line gene editing differs from the somatic cell gene editing used in the highly promising new treatment recently approved for the human disease sickle cell anemia.

关键词： likely Create editing

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mRNA vaccines:a new era in vaccine development

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Oncology Research 2024年第10期32卷 1543-1564页

作者： SHUBHRA CHANDRA jennifer C.WILSON DAVID GOOD MING Q.WEI School of Pharmacy&Medical Sciences Gold Coast campusGriffith UniversityBrisbaneQLD-4222Australia Menzies Health Institute Queensland(MHIQ) Gold Coast CampusGriffith UniversityBrisbaneQLD-4215Australia School of Allied Health Australian Catholic UniversityBrisbaneQLD-4014Australia

The advent of RNA therapy,particularly through the development of mRNA cancer vaccines,has ushered in a new era in the field of *** article provides a concise overview of the key principles,recent advancements,and potential implications of mRNA cancer vaccines as a groundbreaking modality in cancer *** cancer vaccines represent a revolutionary approach to combatting cancer by leveraging the body’s innate immune *** vaccines are designed to deliver specific mRNA sequences encoding cancer-associated antigens,prompting the immune system to recognize and mount a targeted response against malignant *** personalized and adaptive nature of mRNA vaccines holds immense potential for addressing the heterogeneity of cancer and tailoring treatments to individual *** breakthroughs in the development of mRNA vaccines,exemplified by the success of COVID-19 vaccines,have accelerated their application in *** mRNA platform’s versatility allows for the rapid adaptation of vaccine candidates to various cancer types,presenting an agile and promising avenue for therapeutic *** trials of mRNA cancer vaccines have demonstrated encouraging results in terms of safety,immunogenicity,and *** candidates,such as BioNTech’s BNT111 and Moderna’s mRNA-4157,have exhibited promising outcomes in targeting melanoma and solid tumors,*** successes underscore the potential of mRNA vaccines to elicit robust and durable anti-cancer immune *** the field holds great promise,challenges such as manufacturing complexities and cost considerations need to be addressed for widespread *** development of scalable and cost-effective manufacturing processes,along with ongoing clinical research,will be pivotal in realizing the full potential of mRNA cancer ***,mRNA cancer vaccines represent a cutting-edge therapeutic approach that holds the promise of transforming cancer treatment.

关键词： Cancer immunotherapy Immune checkpoint Preventive&therapeutic vaccine Delivery system mRNA

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Pancreatic surgery and tertiary pancreatitis services warrant provision for support from a specialist diabetes team

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World Journal of Diabetes 2024年第4期15卷 598-605页

作者： Vasileios K Mavroeidis jennifer Knapton Francesca Saffioti Daniel L Morganstein Department of HPB Surgery Bristol Royal InfirmaryUniversity Hospitals Bristol and Weston NHS Foundation TrustBristol BS28HWUnited Kingdom Department of Gastrointestinal Surgery Southmead HospitalNorth Bristol NHS TrustBristol BS105NBUnited Kingdom Department of Academic Surgery Royal Marsden NHS Foundation TrustLondon SW36JJUnited Kingdom Department of Gastroenterology and Hepatology Oxford University Hospitals NHS Foundation TrustOxford OX39DUUnited Kingdom UCL Institute for Liver and Digestive Health University College LondonLondon NW32PFUnited Kingdom Department of Endocrinology Chelsea and Westminster Hospital NHS Foundation TrustLondon SW109NHUnited Kingdom Department of Gastrointestinal Unit Royal Marsden NHS Foundation TrustLondon SW36JJUnited Kingdom

Pancreatic surgery units undertake several complex operations,albeit with consi-derable morbidity and mortality,as is the case for the management of complicated acute pancreatitis or chronic *** centralisation of pancreatic surgery services,with the development of designated large-volume centres,has contribu-ted to significantly improved *** this editorial,we discuss the complex associations between diabetes mellitus(DM)and pancreatic/periampullary disease in the context of pancreatic surgery and overall management of complex pancreatitis,highlighting the consequential needs and the indispensable role of specialist diabetes teams in support of tertiary pancreatic *** 3c pan-creatogenic DM,refers to DM developing in the setting of exocrine pancreatic disease,and its identification and management can be challenging,while the glycaemic control of such patients may affect their course of treatment and *** preoperative diabetes assessment is warranted to aid identification of patients who are likely to need commencement or escalation of glucose lowering therapy in the postoperative *** incidence of new onset diabetes after pancreatic resection is widely variable in the literature,and depends on the type and extent of pancreatic resection,as is the case with pancreatic parenchymal loss in the context of severe *** involvement of a specialist diabetes team is essential to ensure a holistic *** the current era,large volume pancreatic surgery services commonly abide by the principles of enhanced recovery after surgery,with inclusion of provisions for optimisation of the perioperative glycaemic control,to improve *** various guidelines are available to aid perioperative management of DM,auditing and quality improvement platforms have highlighted deficiencies in the perioperative management of diabetic patients and areas of required *** need for perioperative support of diabetic

关键词： Pancreatectomy Pancreatoduodenectomy Whipple’s Pancreatitis Diabetes specialist Type 3c pancreatogenic diabetes mellitus

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