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Function and dysfunction of GEMIN5:understanding a novel neurodevelopmental disorder

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Neural Regeneration Research 2024年第11期19卷 2377-2386页

作者： Charles H.nelson Udai b.Pandey Department of Pediatrics Division of Child NeurologyChildren’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA Children’s Neuroscience Institute Children’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding *** the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent *** many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its *** this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder ***,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of *** review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

关键词： cerebellar atrophy GEMIN5 neurodevelopmental disorder neurological disease SMN complex

Gastroesophageal reflux following per-oral endoscopic myotomy:Can we improve outcomes?

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World Journal of Gastroenterology 2024年第22期30卷 2834-2838页

作者： Inian Samarasam Raj Kumar joel Anna b Pulimood Department of Surgery Upper Gastrointestinal Surgery UnitChristian Medical College&HospitalVellore 632004TamilnaduIndia Department of Cardiothoracic Surgery Christian Medical College&HospitalVellore 632004TamilnaduIndia Department of Gastrointestinal Sciences Christian Medical College and HospitalVellore 632004Tamil NaduIndia

This editorial is an analysis the review article by Nabi et al recently published in this *** Cardia is a disease whose pathophysiology is still *** is known that there is inflammation of unknown aetiology leading to loss of ganglion cells in the muscularis *** end result is lower oesophageal sphincter spasm,loss of receptive relaxation,decreased oesophageal peristalsis,all leading on to varying degrees of *** treatment of this condition is palliative in nature,performed by myotomy of the lower oesophagus either surgically or *** reflux disease(GERD)has been associated with the myotomy performed,particularly with the Peroral Endoscopic Myotomy(POEM)*** et al have provided an excellent overview of the latest developments in predicting,preventing,evaluating,and managing GERD subsequent to *** on this theme,this review article explores the concept of using histology of the oesophageal muscle layer,to grade the disease and thereby help tailoring the length/type of myotomy performed during the POEM *** the future,will a histology based algorithm available preoperatively,help modify the POEM procedure,thereby decreasing the incidence of GERD associated with POEM?

关键词： Achalasia cardia Peroral endoscopic myotomy Laparoscopic Heller’s myotomy Histopathology Histologic grading

Storylines of family medicine Ⅶ: family medicine across the lifespan

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Family Medicine and Community Health 2024年第S3期12卷 61-69页

作者： William b Ventres Leslie A Stone Katharine C barnard Sara G Shields Mark J nelson Maria Verónica Svetaz Clara M Keegan joel J Heidelbaugh Paige b beck Lucille Marchand Family and Preventive Medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Family Medicine and Community Health UMass Chan Medical SchoolWorcesterMassachusettsUSA John Peter Smith Hospital Family Medicine Residency Fort WorthTexasUSA Family and Community Medicine Hennepin HealthcareMinneapolisMinnesotaUSA Family Medicine University of Vermont Larner College of MedicineBurlingtonVermontUSA Family Medicine University of Michigan Medical SchoolAnn ArborMichiganUSA Family Medicine and Community Health University of Wisconsin-Madison School of Medicine and Public HealthMadisonWisconsinUSA

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 ***‘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.

关键词： life illustration family

Metallothionein lh Tumor Suppressor Activity in Prostate Cancer Is Mediated by Euchromatin Methyltransferase 1

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Metallothionein lh Tumor Suppressor Activity in Prostate Can...

Decoupling COb>2b> from Climate Change

2012年湖北生物产业发展高端论坛暨湖北省生物工程学会2012年度学术交流会

作者： Han YC Zheng ZL Yu YP Chen R Tseng GC joel b.nelson Luo JH Department of Pathology Biostatistics2 and Urology33550 Terrace StreetUniversity of Pittsburgh School of MedicinePittsburghPA 15261 Department of Pathology Biostatistics2 and Urology33550 Terrace StreetUniversity of Pittsburgh School of MedicinePittsburghPA 15261.

Metallothionein(MT) is a group of metal binding proteins thatare thought to play a role in the detoxification of heavy ***,the biological role and function of MTs remain *** this study,we showed that MT1h,a memberof MT,was widely down-regulated in human malignancies by microarray and validation analyses. Negative expression of MT1h was associated with poor clinical outcomes in both prostate and liver cancer *** promoter region of MTl was hypermethylated in cancer *** of the MT1h promoter in reversed the suppression of MT1h *** expression of MT1h induced cell growth arrest,suppressed colony formation,retarded migration,and reduced *** mice with tumor xenografts with inducible MT1h expressionhad lower tumor volumes as well as fewer metastases and deaths than un-induced ***1h was found tointeract with euchromatin histone methyltransferase 1(EHMT1) and enhanced its methyltransferase activity towards Histone *** down of EHMT1 or a mutation in MT1h that abrogates its interaction with EHMT1 largely eliminated MT1h tumor suppressor *** our knowledge,this study for the first time reveals a novel tumor suppressor activity in a heavy metal binding protein that is dependent on activation of histone methylation.

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International Journal of Geosciences 2024年第3期15卷 246-269页

作者： Michael nelson David b. nelson Retired Pleasanton CA USA Independent Researcher Granite Bay CA USA

This study determines if there is a correlation between rising carbon dioxide levels and global warming. Historical data were reviewed from three different time periods spanning 500 million years. It showed that the curves and trends were too dissimilar to establish a connection. Observations from COb>2b>/temp ratios showed that the COb>2b> and the temperature moved in opposite directions 42% of the time. Many ratios displayed zero or near zero values, reflecting a lack of response. As much as 87% of the ratios revealed negative or near zero values, which strongly negate a correlation. The infrared spectra showed the Greenhouse Gases had an exceptionally low absorption band between 11.67 μm to 9.1 μm, which is a zone called the infrared atmospheric window. Most of the Greenhouse Gases absorb little infrared inside that zone. And that zone is where the Earth’s surface emits almost all infrared radiation. Even with minimal absorbance, water vapor captures the most infrared radiation. It absorbs 84 times more than COb>2b>, 407 thousand times more than methane, 452 thousand times more than ozone and 2.3 million times more than nitrous oxide. The Intergovernmental Panel on Climate Change (IPCC) and the United States EPA excluded water vapor because it was not associated with man-made activities. They reported that water vapor and clouds were simply feedback mechanisms from COb>2b>. Clouds reflect radiation from the sun. The Northern Hemisphere is 2.7°F warmer than the Southern Hemisphere because of clouds. The world cloud cover has gone down 4.1% from 1982 to 2018. Calculations show that this could be responsible for 2.4°F of the 2.7°F. The research shows that most of the recent increase in temperature (89.9%) is because of fewer clouds.

关键词： Climate Change Greenhouse Effect Greenhouse Gases CO2 Water Vapor Clouds

The Cloud Model for Climate Change

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International Journal of Geosciences 2024年第5期15卷 366-395页

作者： Michael nelson David b. nelson Retired Pleasanton CA USA

In 1995, the Intergovernmental Panel on Climate Change (IPCC) released a thermodynamic model based on the Greenhouse Effect, aiming to forecast global temperatures. This study delves into the intricacies of that model. Some interesting observations are revealed. The IPCC model equated average temperatures with average energy fluxes, which can cause significant errors. The model assumed that all energy fluxes remained constant, and the Earth emitted infrared radiation as if it were a blackbody. Neither of those conditions exists. The IPCC’s definition of Climate Change only includes events caused by human actions, excluding most causes. Satellite data aimed at the tops of clouds may have inferred a high Greenhouse Gas absorption flux. The model showed more energy coming from the atmosphere than absorbed from the sun, which may have caused a violation of the First and Second Laws of Thermodynamics. There were unexpectedly large gaps in the satellite data that aligned with various absorption bands of Greenhouse Gases, possibly caused by photon scattering associated with re-emissions. based on science, we developed a cloud-based climate model that complied with the Radiation Laws and the First and Second Laws of Thermodynamics. The Cloud Model showed that 81.3% of the outgoing reflected and infrared radiation was applicable to the clouds and water vapor. In comparison, the involvement of COb>2b> was only 0.04%, making it too minuscule to measure reliably.

关键词： Climate Change Greenhouse Gas CO2 Clouds Model Thermodynamics

A neural branch-and-price for truck scheduling in cross-docks

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Science China Mathematics 2024年第6期67卷 1341-1358页

作者： Rahimeh Neamatian Monemi Shahin Gelareh nelson Maculan Wei-Kun Chen Sharkey Predictim Globe Villeneuve d’Ascq59650France Département R&T IUT de BéthuneUniversitéd’ArtoisBéthuneF-62000France Federal University of Rio de Janeiro COPPE-PESCRio de JaneiroRJ 21941-972Brazil School of Mathematics and Statistics Beijing Institute of TechnologyBeijing100081China

In this paper,we address the complex problem of dock-door assignment and truck scheduling within cross-docking *** is a problem that requires frequent resolution throughout the operational day,as disruptions often invalidate the optimal *** the problem's highly combinatorial nature,finding an optimal solution demands significant computational time and ***,the distribution of data across problem instances over a lengthy planning horizon remains consistently stable,with minimal concern regarding distribution *** factors collectively establish the problem as an ideal candidate for a learn-to-optimize solution *** propose a Dantzig-Wolfe reformulation,solving it via both a conventional branch-and-price approach and a neural branch-and-price approach,the latter of which employs imitation ***,we introduce some classes of valid inequalities to enhance and refine the pricing problem through a branch-and-cut *** computational experiments demonstrate that this methodology is not only feasible but also presents a viable alternative to the traditional branch-and-price algorithms typically utilized for such challenges.

关键词： cross-docking MILP modeling Dantzig-Wolfe decomposition graph convolutional network

The Impacts and Causes of Land Fragmentation on Farm Productivity: Case Review of East African Countries

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Open Journal of Ecology 2024年第5期14卷 455-482页

作者： Joseph Mayindo Mayele Jacob b. Kolleh joel Emmanuel Saburi Department of Agricultural and Resource Economics The University of Tokyo Tokyo Japan Department of Forestry and Wildlife College of Natural Resources and Environmental Studies University of Juba Juba South Sudan Department of Socio-Economic and Applied Statistics Central Agricultural Research Institute (CARI) Suakoko Liberia

This report provides an overall assessment of land fragmentation problems in East Africa. Many parts of East Africa have become highly fragmented, putting development systems and activities in these areas at risk of complete collapse. Land fragmentation occurs when land gets converted for agriculture, industrialization, or urbanization, invaded by non-local plants, or enclosed for individual use and by subdividing farmlands into subsequent smaller units called parcels with varying average farm sizes. Fragmentation results from inappropriate agricultural development processes and ineffective land use planning that fails to recognize how farmland is used, and the importance of its interconnected areas. Insecurity of tenure and resource rights are key factors in making this possible. Land fragmentation is one of the key reasons why the ability of most resources in East Africa becomes scarcer, and those remaining become “privatized” by more powerful community members—keen to maintain their access to them. Such individualistic attitudes are new and disadvantage the poorest even further by affecting the traditional customary safety nets and agricultural outputs. Neither the government nor customary governance systems effectively protect resource access for the poorest. This review summary report identifies the key causes, measures, and implications, government interventions, and the common remedies to land fragmentation problems in the East African Countries of Kenya, Uganda, Rwanda, and Tanzania including neighboring Ethiopia, and the Sudan. The findings indicated from 2005 to 2015, the population kept increasing for all the named countries in East Africa with Rwanda and Uganda having a substantial increase in population density. The study review further explores the trend in the performance of agriculture by average farm sizes within the intervals of five years by highlighting their strong linkages and found that the average farm size has declined drastically, especiall

关键词： Land Fragmentation Land Consolidation Farm Productivity Industrialization Impacts Causes Average Farm Size Population East Africa

Wheat zinc finger protein TaZF interacts with both the powdery mildew AvrPm2 protein and the corresponding wheat Pm2a immune receptor

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Plant Communications 2024年第5期5卷 25-41页

作者： beatrice Manser Helen Zbinden Gerhard Herren joel Steger Jonatan Isaksson Stephanie braunlich Thomas Wicker beat Keller Department of Plant and Microbial biology University of ZurichZollikerstrasse 1078008 ZurichSwitzerland Agroscope Route de Duillier 501260 NyonSwitzerland bIOREbA AG Christoph Merian-Ring 74153 ReinachSwitzerland

Plant defense responses to pathogens are induced after direct or indirect perception of effector proteins or their activity on host *** fungal–plant interactions,relatively little is known about whether,in addi-tion to avirulence effectors and immune receptors,other proteins contribute to specific *** nucleotide-binding leucine-rich repeat(NLR)immune receptor Pm2a in wheat recognizes the fungal pow-dery mildew effector *** found that the predicted wheat zincfinger TaZF interacts with both the fungal avirulence protein AvrPm2 and the wheat NLR *** further demonstrated that the virulent AvrPm2-H2 variant does not interact with *** silencing in wheat resulted in a reduction but not a loss of Pm2a-mediated powdery mildew *** studies showed that the leucine-rich repeat domain of Pm2a is the mediator of the interaction with *** recruits both Pm2a and AvrPm2 from the cytosol to the nucleus,resulting in nuclear localization of Pm2a,TaZF,and AvrPm2 in *** propose that TaZF acts as a facilitator of Pm2a-dependent AvrPm2 effector *** highlight the importance of identifying effector host targets for characterization of NLR-mediated effector recognition.

关键词： plant immunity plant-fungal interactions pathogen effectors nucleotide-binding leucine-rich repeat immune receptor NLR wheat powdery mildew