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Rare genetic variants in ARID2are responsible for a recently described neurodevelopmental condition called ARID2-related disorder (ARID2-RD). ARID2 belongs to PBAF, a unit of the SWI/SNF complex, which is a chromatin remodeling complex. This work aims to further delineate the phenotypic spectrum of ARID2-RD, providing clinicians with additional data for better care and aid in the future diagnosis of this condition. We obtained the genotypes and phenotypes of 27 previously unreported individuals with ARID2-RD and compared this series with findings in the literature. We also assessed peripheral blood DNA methylation profiles in individuals with ARID2-RD compared to episignatures of controls, unresolved cases, and other neurodevelopmental disorders. The main clinical features of ARID2-RD are developmental delay, speech disorders, intellectual disability (ID), behavior problems, short stature, and various dysmorphic and ectodermal features. Genome-wide differential methylation analysis revealed a global hypermethylated profile in ARID2-RD that could aid in reclassifying variants of uncertain significance. Our study doubles the number of reported individuals with ARID2pathogenic variants to 53. It confirms loss-of-function as a pathomechanism and shows the absence of a clear genotype-phenotype correlation. We provide evidence for a unique DNA methylation episignature for ARID2-RD and further delineate the ARID2-associated phenotype.

A SYSTEMS APPROACH TO SEED SELECTION Imagine the day you can provide details about each specific field to your seed supplier and they take that information to custom-build the perfect [...]

Hypoxia is more and more perceived as pivotal physiological driving force, allowing cells in the brain and elsewhere to acclimate to lowered oxygen (O2), and abridged metabolism. The mediating transcription program is induced by inspiratory hypoxia but also by intensive motor‐cognitive tasks, provoking a relative decrease in O2in relation to the acutely augmented requirement. We termed this fundamental, demand‐dependent drop in O2availability “functional hypoxia.” Major players in the hypoxia response are hypoxia‐inducible factors (HIFs) and associated prolyl‐hydroxylases. HIFs are transcription factors, stabilized by low O2accessibility, and control expression of a multitude of genes. Changes in oxygen, however, can also be sensed via other pathways, among them the thiol‐oxidase (2‐aminoethanethiol) dioxygenase. Considering the far‐reaching biological response to hypoxia, hitherto mostly observed in rodents, we initiated a translational project, combining mild to moderate inspiratory with functional hypoxia. We had identified this combination earlier to benefit motor‐cognitive attainment in mice. A total of 20 subjects were included: 13 healthy individuals and 7 patients with depression and/or autism spectrum disorder. Here, we show that motor‐cognitive training under inspiratory hypoxia (12% O2) for 3.5 h daily over 3 weeks is optimally tolerated. We present first signals of beneficial effects on general well‐being, cognitive performance, physical fitness and psychopathology. Erythropoietin in serum increases under hypoxia and flow cytometry analysis of blood reveals several immune cell types to be mildly modulated by hypoxia. To obtain reliable information regarding the “add‐on” value of inspiratory on top of functional hypoxia, induced by motor‐cognitive training, a single‐blind study—with versus without inspiratory hypoxia—is essential and outlined here. Motor‐cognitive training under inspiratory hypoxia (12% O2) for 3.5 h daily over 3 weeks is very well tolerated by healthy individuals as well as by patients with depression and/or autism spectrum disorder.We find first promising signals of beneficial effects on general well‐being, cognitive performance, physical fitness, and psychopathology.Our protocol of motor‐cognitive training under inspiratory hypoxia does not adversely affect the mononuclear cell composition in the blood of adults.To obtain reliable information regarding the “add‐on” value of mild to moderate inspiratory on top of functional hypoxia, induced by motor‐cognitive training, the planned single‐blind study—with versus without inspiratory hypoxia—is required. Motor‐cognitive training under inspiratory hypoxia (12% O2) for 3.5 h daily over 3 weeks is very well tolerated by healthy individuals as well as by patients with depression and/or autism spectrum disorder. We find first promising signals of beneficial effects on general well‐being, cognitive performance, physical fitness, and psychopathology. Our protocol of motor‐cognitive training under inspiratory hypoxia does not adversely affect the mononuclear cell composition in the blood of adults. To obtain reliable information regarding the “add‐on” value of mild to moderate inspiratory on top of functional hypoxia, induced by motor‐cognitive training, the planned single‐blind study—with versus without inspiratory hypoxia—is required.

Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, a 3-year prospective study, we evaluated a novel diagnostic concept based on multidisciplinary expertise in Germany. Here we present the systematic investigation of the phenotypic and molecular genetic data of 1,577 patients who had undergone exome sequencing and were partially analyzed with next-generation phenotyping approaches. Molecular genetic diagnoses were established in 32% of the patients totaling 370 distinct molecular genetic causes, most with prevalence below 1:50,000. During the diagnostic process, 34 novel and 23 candidate genotype–phenotype associations were identified, mainly in individuals with neurodevelopmental disorders. Sequencing data of the subcohort that consented to computer-assisted analysis of their facial images with GestaltMatcher could be prioritized more efficiently compared with approaches based solely on clinical features and molecular scores. Our study demonstrates the synergy of using next-generation sequencing and phenotyping for diagnosing ultrarare diseases in routine healthcare and discovering novel etiologies by multidisciplinary teams.

2019 SPECIAL REPORT CORN Aug. 1 USDA Change from Tour Change Yield Estimate (*) 2018 Final Yield (**) from 2018 Illinois 181 -13.8% 171.17 -11.1% Indiana 166 -12.2% 161.46 -11.5% [...]

Ten years ago, Ernest Hallock bought seed from just one multinational company. This spring, he and his son-in-law, Erik Johnson, planted four seed brands-a number that fluctuates each year and [...]

Ahead of the 2020 Pro Farmer Crop Tour, crop condition ratings were strong. Yet, dryness was expanding across areas of the Corn Belt. A team of crop scouts set out [...]

If you haven't been following the news since early June, get ready for a few big surprises. Over-the-top dicamba products, Engenia, FeXapan and XtendMax spent time under the court's microscope, [...]

With each tractor or combine pass, pig squeal and kernel placed in the soil, Brian Washburn is thankful for the life he's created on the farm. It was a life [...]

What would you do with one silver bullet that allowed complete control over a single pest that plagues your fields? Would you use it against insects, weeds, diseases or nematodes? [...]

With Christmas just around the corner, you might be venturing out to find that perfect Christmas tree. Not too tall, short or wide, it has to fit just right in [...]

Seed companies invest billions in R&D annually to bring new genetics, traits and more to your farm. We want to introduce you to a few of the faces behind the [...]

According to the plain realities of farming, conservation agriculture's yardstick is efficacy and profit. For the following, featured farms, conservation and financial success are a wedded pair. Each of these [...]

While mostly de novo truncating variants in SCAF4were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder. The molecular spectrum comprises 25 truncating, eight splice-site and five missense variants. While all other truncating variants were classified as pathogenic/likely pathogenic, significance of one C-terminal truncating variant, one splice-site variant and the missense variants remained unclear. Three missense variants in the CTD-interacting domain of SCAF4 were predicted to destabilize the domain. Twenty-three variants occurred de novo, and variants were inherited in 13 cases. Frequent clinical findings were mild developmental delay with speech impairment, seizures, and skeletal abnormalities such as clubfoot, scoliosis or hip dysplasia. Cognitive abilities ranged from normal IQ to severe intellectual disability (ID), with borderline to mild ID in the majority of individuals. Our study confirms the role of SCAF4variants in neurodevelopmental disorders and further delineates the associated clinical phenotype.

Innere, sog. zirkadiane Uhren regulieren zahlreiche Körperfunktionen – darunter unseren Schlaf-Wach-Rhythmus – im 24-h-Takt. Während die Funktion des zirkadianen Systems in der Regulation der Phasenlage des Schlafs (Prozess C) lange bekannt war, zeigen neuere Studien eine weit engere Verknüpfung von Uhrensystem und Schlaffunktion auf mehreren Ebenen. Genetische Defekte im molekularen Uhrwerk haben Auswirkungen auf den Schlafhomöostat (Prozess S). Umgekehrt wirken Änderungen im natürlichen Schlafzyklus zurück auf die Funktion der zirkadianen Uhr – und das nicht nur im zentralen Nervensystem (ZNS), sondern insbesondere auch in peripheren Organen. Dieser Schlaf-Uhr-Crosstalk könnte viele der negativen Effekte von Rhythmus- und Schlafstörungen auf den Energiestoffwechsel erklären. Gleichzeitig bietet er neue Ansatzpunkte für die Prävention und Behandlung von schlafassoziierten pathologischen Effekten, z. B. bei Schichtarbeitern. Dieser Übersichtsartikel beschreibt die Interaktion von Uhrensystem und Schlaf-Regelkreisen im ZNS und deren Effekte auf periphere physiologische Prozesse, insbesondere den Energiestoffwechsel. Er skizziert ein Modell der engen Kopplung von Schlaf und Uhrenfunktion und deren Bedeutung als Angriffspunkt für die Behandlung von durch Schlafstörungen bedingte Erkrankungen.

Zusammenfassung: Der kleine, inzidentell entdeckte Nierentumor stellt ein häufiges Problem in der klinischen Routinediagnostik dar. Zwar werden kleine Nierentumoren durch die leistungsfähigen, modernen Schnittbildverfahren immer häufiger entdeckt, die eindeutige Zuordnung der Dignität dieser Läsionen ist anhand der Bildgebung jedoch nicht immer zu gewährleisten. In der Hoffnung, eine minimal-invasive, histologische Klärung zu erzielen und die Zahl unnötiger operativer Eingriffe zu minimieren, wird der Ruf nach der perkutanen Biopsie kleiner Nierentumoren in den letzten Jahren zunehmend lauter. Der vorliegende Beitrag erläutert den aktuellen Stellenwert der perkutanen Biopsie kleiner Nierenraumforderungen unter besonderer Berücksichtigung der Entwicklung neuer histopathologischer Analyseverfahren, technischer Aspekte der Stanzbiopsie und der Zuverlässigkeit der Diagnosefindung. Darüber hinaus werden die Indikationen zur Stanzbiopsie kleiner Nierentumoren vor dem Hintergrund der aktuellen Literatur erörtert.

Zusammenfassung: Einleitung: Die Sakroplastie stellt ein noch junges Verfahren zur perkutanen Zementapplikation bei schmerzhafter Insuffizienzfraktur oder tumoröser Läsion dar. Bislang liegen noch keine standardisierten Untersuchungen zu den Ergebnissen, insbesondere zur Zementaustrittsrate, vor. Zielsetzung der vorgelegten Studie war, in einem kontrollierten Experiment Praktikabilität und Ergebnisse der ballonassistierten, CT-gesteuerten Zementapplikation zu eruieren. Material und Methoden: Die Versuche wurden an fixierten Spenderleichen (n=6) vorgenommen. Die Zementapplikation erfolgte rechtsseitig unter Verwendung insufflierbarer Ballons (Kyphon), auf der Gegenseite in konventioneller Technik. Zur präoperativen Planung und postoperativen Auswertung wurde jeweils ein Spiral-CT (Philips Brilliance 64) durchgeführt. Intraoperativ wurde die Prozedur durch einzelne Durchleuchtungsbilder im „CT-Fluoro“-Modus gesteuert. Ergebnisse: Während der Prozeduren traten keine technischen Probleme auf. Die durchschnittliche Operationszeit betrug 36,9±2,4 min (Spannweite 33,1–38,9) pro Präparat. Mit dem gewählten CT-Protokoll resultierten folgende Effektivdosen: 0,99 mSv (weiblich) respektive 0,63 mSv (männlich) pro Scan sowie 0,33 mSv (weiblich) und 0,25 mSv (männlich) pro Durchleuchtungsbild. Ein extraossärer Zementaustritt wurde weder bei der ballonassistierten noch bei der konventionellen Applikation beobachtet. Schlussfolgerung: Die CT-gesteuerte Sakroplastie wies in unserer Studie eine gute Praktikabilität und hohe Präzision bei vertretbarer Strahlenexposition auf. Klinische Studien werden allerdings erst zeigen müssen, in wieweit das vorgestellte, ballonassistierte Verfahren der konventionellen Technik hinsichtlich der Zementaustrittsrate überlegen ist. Außerdem wird die analgetische Effizienz des Verfahrens zu prüfen sein.

Das an der FH Münster angebotene Lehrprojekt "Ich sehe was, was Du nicht siehst - ungewohnte Perspektiven im Versorgungshandeln" schaut - im wahren Sinne des Wortes - auf nähe-kritische Versorgungssituationen, indem es den Fokus auf die visuelle Nähe lenkt und durch die Arbeit mit Fotografie einen Perspektivwechsel anstößt, um die Studierenden in ihrem Reflexionsprozess zu begleiten. Ziel ist es, für das Thema "Nähe und Distanz" zu sensibilisieren und interaktive Kompetenzen zu stärken. Zudem kommt das Projekt den Forderungen nach einer verstärkten Selbsterfahrung und Reflexion im Rahmen der Ausbildung von Pflegefachkräften nach.

In-season management is critical to help maximize yield on every acre, and benchmarking a product or practice is necessary when making input decisions for the following year. During the season [...]

Diversity helps spread risk. Are you as diverse as you think? When you glance across your corn and soybean fields, the marker of a good crop is uniformity. Row after [...]

It's midseason--the critical summer growth window of July and August--and it's time for you to do the proactive management and scouting that can help save your crops, and pocketbook, from [...]

There was a time when Doug Winter wouldn't have blinked at the site of a little waterhemp in his fields. After the steep rise in resistance, the southeastern Illinois corn [...]

It won't take long to notice when resistant weeds set up camp in your fields. When they tower over your corn or soybeans, rob yields and double or triple your [...]

In der Luftfahrt kommen hochfeste Schichtverbundwerkstoffe zum Einsatz, welche zumeist im Nietverfahren gefügt werden. Dies erfordert eine vorausgehende Bohrbearbeitung des Werkstoffverbunds. Da die beiden Einzelwerkstoffe meist gegensätzliche Bohrparameter erfordern (z. B. Titan und CFK) kommen derzeit Kompromissparameter zum Einsatz. Die Fertigungsqualität ist dadurch beschränkt und der Werkzeugverschleiß hoch. Dieser Beitrag stellt eine wirkleistungsbasierte Bohrprozesssteuerung vor, welche die materialspezifische Umschaltung der Prozessparameter ermöglicht. Die Detektionslogik basiert auf dem dynamischen Anteil der Spindelwirkleistung und erweist sich in mehreren Bohrserien als präzise und robust. Zudem ist eine erhöhte Fertigungsqualität zu verzeichnen.

IMPORTANCE: Psychotic symptoms greatly increase the burden of disease for people with neurodegenerative disorders and their caregivers. Cholinesterase inhibitors (ChEIs) may be effective treatment for psychotic symptoms in these disorders. Previous trials only evaluated neuropsychiatric symptoms as a secondary and an overall outcome, potentially blurring the outcomes noted with ChEI use specifically for psychotic symptoms. OBJECTIVE: To quantitatively assess the use of ChEIs for treatment of individual neuropsychiatric symptoms, specifically hallucinations and delusions, in patients with Alzheimer disease (AD), Parkinson disease (PD), and dementia with Lewy bodies (DLB). DATA SOURCES: A systematic search was performed in PubMed (MEDLINE), Embase, and PsychInfo, without year restrictions. Additional eligible studies were retrieved from reference lists. The final search cutoff date was April 21, 2022. STUDY SELECTION: Studies were selected if they presented the results of placebo-controlled randomized clinical trials, including at least 1 donepezil, rivastigmine, or galantamine treatment arm in patients with AD, PD, or DLB; if they applied at least 1 neuropsychiatric measure including hallucinations and/or delusions; and if a full-text version of the study was available in the English language. Study selection was performed and checked by multiple reviewers. DATA EXTRACTION AND SYNTHESIS: Original research data were requested on eligible studies. A 2-stage meta-analysis was then performed, using random-effects models. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed for extracting data and assessing the data quality and validity. Data extraction was checked by a second reviewer. MAIN OUTCOMES AND MEASURES: Primary outcomes were hallucinations and delusions; secondary outcomes included all other individual neuropsychiatric subdomains as well as the total neuropsychiatric score. RESULTS: In total, 34 eligible randomized clinical trials were selected. Individual participant data on 6649 individuals (3830 [62.6%] women; mean [SD] age, 75.0 [8.2] years) were obtained from 17 trials (AD: n = 12; PD: n = 5; individual participant data were not available for DLB). An association with ChEI treatment was shown in the AD subgroup for delusions (−0.08; 95% CI, −0.14 to −0.03; P = .006) and hallucinations (−0.09; 95% CI, −0.14 to −0.04; P = .003) and in the PD subgroup for delusions (−0.14; 95% CI, −0.26 to −0.01; P = .04) and hallucinations (−0.08, 95% CI −0.13 to −0.03; P = .01). CONCLUSIONS AND RELEVANCE: The results of this individual participant data meta-analysis suggest that ChEI treatment improves psychotic symptoms in patients with AD and PD with small effect sizes.

The last thing your pesticides or fertilizers touch is the nozzle tip--and the wrong nozzle or a worn nozzle could lead to lost dollars and poor performance. 'Nozzle selection is [...]

Next year, things have to be different, says Forest City, Iowa, farmer Doug Tweeten. This past summer he, and thousands of U.S. farmers, walked into cupped, crinkled soybean fields with [...]

As a landowner, when making management decisions about my land I consider: 1=Strongly Disagree 5=Strongly Agree Soil quality 4.19 Needs of the farm operator leasing my land 4.12 Future generations [...]

Weeds resist, insects persist and fungus continues to grow-that is, unless stewardship is practiced and new tools are introduced. One of the biggest barriers to introducing new pesticides, which includes [...]

After years of planning, sketching, discussing and finally quoting prices, Dennis Ivers and his family built their dream shop. The Illinois corn and soybean farmers had made do with the [...]

Fifteen grams of soil can describe a microbiome profile using DNA sequencing for better crop decisions. Think of it as a genetic test just like the cheek swab for DNA [...]

Arysta LifeScience is under new ownership as former parent company Platform Specialty Products sold it for $4.2 billion to UPL Limited. The transaction was first signed in July 2018, and [...]

The Environmental Protection Agency has granted registration for Duromide, Koch's new active ingredient in Anvol nitrogen stabilizer. With the registration under the Toxic Substances Control Act, Anvol ammonia volatilization inhibitor [...]

Unseen by the naked eye, there are enough microbials to circle the earth 10 to the 30lh power times, according to Novozymes. These tiny organisms, also known as biologicals, could [...]

It's not news to you that the ag industry has been in a tight spot financially for the past several years--and 2019 looks to offer more of the same. 'I [...]

Farmers will have new defenses against problem weeds this year, with more options to come as technology is fine-tuned. That's good news because weeds are constantly evolving. Here are five [...]

It's natural to focus on spring and summer forecasts when the growing season is underway, but winter weather can have a big impact on crops, too. This season, meteorologists have [...]

Timing big-dollar input purchases is always important, but this year it could mean the difference between saving some dollars or breaking your budget. Here's a look at what you can [...]

If farmers from just 50 years ago could see what you do today, they would stand in awe. Precision farming maximizes each acre within inches, seeds withstand herbicide and insects, [...]

When you buy a new car, you buy insurance to protect it. The same can be said about seeds. When agriculturalists discovered their irreplaceable value, they realized seeds needed to [...]

In July and August it's not uncommon to see corn and soybean diseases rear their ugly heads. Learn how to identify key diseases and what, if any, action you can [...]

Bacterial abortive-infection systems limit the spread of foreign invaders by shutting down or killing infected cells before the invaders can replicate1,2. Several RNA-targeting CRISPR–Cas systems (that is, types III and VI) cause abortive-infection phenotypes by activating indiscriminate nucleases3–5. However, a CRISPR-mediated abortive mechanism that leverages indiscriminate DNase activity of an RNA-guided single-effector nuclease has yet to be observed. Here we report that RNA targeting by the type V single-effector nuclease Cas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA (dsDNA). After recognizing an RNA target with an activating protospacer-flanking sequence, Cas12a2 efficiently degrades single-stranded RNA (ssRNA), single-stranded DNA (ssDNA) and dsDNA. Within cells, the activation of Cas12a2 induces an SOS DNA-damage response and impairs growth, preventing the dissemination of the invader. Finally, we harnessed the collateral activity of Cas12a2 for direct RNA detection, demonstrating that Cas12a2 can be repurposed as an RNA-guided RNA-targeting tool. These findings expand the known defensive abilities of CRISPR–Cas systems and create additional opportunities for CRISPR technologies.

Wet weather brought a myriad of problems in 2019. Aside from planting and harvest delays, it helped spread diseases, many of which could show up again in 2020. If you [...]

If you are intentional about soil health, your land might be worth more. Plus, if you can prove to your landlord your actions are increasing his or her land value, [...]

As a polar vortex tore through the Midwest and northern Plains, frigid temperatures were among the least of 25-year-old Tanner Overby's worries. His life changed forever on that cold Jan. [...]

Imagine you have four daughters, it's nearly Christmas and you still need to buy presents, explains Erich Eller, owner of Forefront Ag Solutions. One daughter sees a sweater she loves [...]

Imagine starting from scratch today. You'd have to buy equipment, secure land, identify input suppliers-and, of course, find a way to pay for it all. It's no easy task, but [...]

He set up each tight with care, double checked the watering rates and took one last look at the soybeans. This was it-this had to work. In 1966, when every [...]