Neuroinflammation can positively influence axon regeneration following injury in the central nervous system. Inflammation promotes the release of neurotrophic molecules and stimulates intrinsic proregenerative molecular machinery in neurons, but the detailed mechanisms driving this effect are not fully understood. We evaluated how microRNAs are regulated in retinal neurons in response to intraocular inflammation to identify their potential role in axon regeneration. We found that miR-383-5p is downregulated in retinal ganglion cells in response to zymosan-induced intraocular inflammation. MiR-383-5p downregulation in neurons is sufficient to promote axon growth in vitro, and the intravitreal injection of a miR-383-5p inhibitor into the eye promotes axon regeneration following optic nerve crush. MiR-383-5p directly targets ciliary neurotrophic factor (CNTF) receptor components, and miR-383-5p inhibition sensitizes adult retinal neurons to the outgrowth-promoting effects of CNTF. Interestingly, we also demonstrate that CNTF treatment is sufficient to reduce miR-383-5p levels in neurons, constituting a positive-feedback module, whereby initial CNTF treatment reduces miR-383-5p levels, which then disinhibits CNTF receptor components to sensitize neurons to the ligand. Additionally, miR-383-5p inhibition derepresses the mitochondrial antioxidant protein peroxiredoxin-3 (PRDX3) which was required for the proregenerative effects associated with miR-383-5p loss-of-function in vitro. We have thus identified a positive-feedback mechanism that facilitates neuronal CNTF sensitivity in neurons and a new molecular signaling module that promotes inflammation-induced axon regeneration.

The superior colliculus receives a direct projection from retinal ganglion cells. In primates, it remains unknown if the same ganglion cells also supply the lateral geniculate nucleus. To address this issue, a double-label experiment was performed in two male macaques. The animals fixated a target while injection sites were scouted in the superior colliculus by recording and stimulating with a tetrode. Once suitable sites were identified, cholera toxin subunit B-Alexa Fluor 488 was injected via an adjacent micropipette. In a subsequent acute experiment, cholera toxin subunit B-Alexa Fluor 555 was injected into the lateral geniculate nucleus at matching retinotopic locations. After a brief survival period, ganglion cells were examined in retinal flatmounts. The percentage of double-labeled cells varied locally, depending on the relative efficiency of retrograde transport by each tracer and the precision of retinotopic overlap of injection sites in each target nucleus. In counting boxes with extensive overlap, 76–98% of ganglion cells projecting to the superior colliculus were double labeled. Cells projecting to the superior colliculus constituted 4.0–6.7% of the labeled ganglion cell population. In one particularly large zone, there were 5,746 cells labeled only by CTB-AF555, 561cells double labeled by CTB-AF555 and CTB-AF488, but no cell labeled only by CTB-AF488. These data indicate that retinal input to the macaque superior colliculus arises from a collateral axonal branch supplied by ~5% of the ganglion cells that project to the lateral geniculate nucleus. Surprisingly, there exist no ganglion cells that project exclusively to the SC.

The establishment of neural connectivity is a major part of neural development. The central nervous system (CNS) midline is the most characterized axon guidance choice point, and work in Drosophila has played a pivotal role in understanding the molecular mechanisms responsible. Axons respond to attractive cues such as Netrin via the Frazzled receptor, and repulsive cues such as Slit via Robo receptors. Both signals are expressed at the CNS midline, affect pioneer axons, and have dramatic effects on the axon scaffold as a whole. Here, we focus on previous research analyzing classic mutants in the Slit/Robo pathway, which can readily be detected with a dissecting microscope. We also discuss analyzing these mutants in a teaching lab situation. The combination of sophisticated genetics and reliable axonal markers in Drosophila allows phenotypic analysis to be performed at the single-cell level. The elaborate architecture of neurons is very sensitive to disruption by genetic mutations, allowing the effects of novel mutations to be easily detected and assessed.

These two Arbitration Original Petitions have been filed under Section 34(2)(b)(ii) and Section 34 (2-A) of the Arbitration and Conciliation Act, 1996 wherein the Impugned Arbitral Awards both dated 22.04.2022 have been challenged.

_____________ https://www.mhc.tn.gov.in/judis Arb.O.P.(Com.Div.)Nos.646 & 647 of 2022

2. The Respondent herein was the claimant before the Arbitral Tribunal and had filed two claims in respect of Chimney No.I and Chimney No.II under Work Order No.AXON/WO/017/2010-2011 (Chimney No.I) dated 09.08.2010 and Work Order No.AXON/WO/019/2010-2011 (Chimney No.II) dated 21.08.2010 respectively.

Manchester : Manchester University Press, [2017]

Oxford : Archaeopress Publishing Ltd, [2015]

Manchester : Manchester University Press, [2020]

Archives, Room Use Only - HE243.M55 1924

The remora's sucker disc is "one of the most remarkable and most highly modified skeletal structures among vertebrates."

The post New study proves the remora’s sucker disc is in fact a highly modified dorsal fin / Q&A with taxonomist David Johnson appeared first on Smithsonian Insider.

Aline A. Alves, Heloisa B. Gabriel, Maria J. R. Bezerra, Wanderley de Souza, Sue Vaughan, Narcisa L. Cunha-e-Silva, and Jack D. Sunter

Eukaryotic flagella are complex microtubule based organelles and in many organisms there are extra-axonemal structures present, including the outer dense fibres of mammalian sperm and the paraflagellar rod (PFR) of trypanosomes. Flagellum assembly is a complex process occurring across three main compartments, the cytoplasm, the transition fibre-transition zone, and the flagellum. It begins with translation of protein components, followed by their sorting and trafficking into the flagellum, transport to the assembly site and then incorporation. Flagella are formed from over 500 proteins; the principles governing axonemal component assembly are relatively clear. However, the coordination and sites of extra-axonemal structure assembly processes are less clear.

We have discovered two cytoplasmic proteins in T. brucei that are required for PFR formation, PFR assembly factors 1 and 2. Deletion of either PFR-AF1 or PFR-AF2 dramatically disrupted PFR formation and caused a reduction in the amount of major PFR proteins. The presence of cytoplasmic factors required for PFR formation aligns with the concept of processes occurring across multiple compartments to facilitate axoneme assembly and this is likely a common theme for extra-axonemal structure assembly.

Aline A. Alves
Apr 15, 2020; 0:jcs.242271v1-jcs.242271
Articles

Polycyclic aromatic hydrocarbons (PAHs) are a large group of toxic molecules produced by forest fires, industrial processes and the incomplete combustion of fossil fuels. The airborne particles containing these molecules are often washed into watercourses, where they can persist. This study uses long-term monitoring data from the Elbe river, Saxony, Germany, to show how changes in PAH sources affect both the concentrations of these chemicals and the corresponding environmental risks. The researchers suggest that controlling PAHs is the best prevention of harm to aquatic and human health.

IT USED to be known as the largest village in England.

 Remember these guys, well they finally made it to the flocking stage. Like the ECW forces, I based these as if on a rough field so hit them with the layers of brown flock. I was hoping the long green grass will make up for the lack of base detail. Although saying that, I did sprinkle a few pinches of rough sand onto the glued base before the flock, this did give it some stoney detail. This seemed to work well so next time I will add a little more.

I want my units in Dux Bellurom to be quite large so I increased the base size to a whopping 120x80mm. This should give enough room for nice dioramas and cavalry formations. I love this era and it’s nice to have burning away on the back burner.
 I still need to touch up the banner a remove the grass from the figures, but now they are done and can make room for others.

 I took these beautiful images from a Dark ages Facebook page for reference latter on with painting. Thank you Jack Sarge for posting them.

Christophe Leterrier
Feb 28, 2018; 38:2135-2145
Viewpoints

WD Knowles
Nov 1, 1981; 1:1236-1241
Articles

The opossum-sized mammal lived in Madagascar at the end of the age of the dinosaurs

Ceftriaxone at therapeutic doses can lead to renal stone formation.

Renal stone formation with ceftriaxone therapy can result in postrenal acute renal failure in children. The condition can be treated effectively by timely pharmacotherapy or retrograde ureteral catheterization with good prognosis. (Read the full article)

Background: Intensive care unit (ICU) patients may experience ceftriaxone underexposure but clinical outcomes data are lacking. The objective of this study was to determine the impact of ceftriaxone dosing on clinical outcomes amongst ICU patients without central nervous system (CNS) infection.

Methods: A retrospective study of ICU patients receiving intravenous, empiric ceftriaxone for non-CNS infections was conducted. Patients ≥18 years of age who received ≤2 grams of ceftriaxone daily for ≥72 hours were included and categorized as receiving ceftriaxone 1 gram or 2 grams daily. The primary, composite outcome was treatment failure: inpatient mortality and/or antibiotic escalation due to clinical worsening. Propensity score matching was performed based on the probability of receiving ceftriaxone 2 grams daily. Multivariable logistic regression determined the association between ceftriaxone dose and treatment failure in a propensity-matched cohort.

Results: A total of 212 patients were included in the propensity-matched cohort. The most common diagnoses (83.0%) were pneumonia and urinary tract infection. Treatment failure occurred in 17.0% and 5.7% of patients receiving 1 gram and 2 grams daily, respectively (p=0.0156). Overall inpatient mortality was 8.5%. Ceftriaxone 2 gram dosing was associated with a reduced likelihood of treatment failure (adjusted odds ratio=0.190; 95% confidence interval: 0.059 – 0.607). Other independent predictors of treatment failure included sequential organ failure assessment score (aOR 1.440, 95% CI 1.254 – 1.653) and creatinine clearance at 72 hours from ceftriaxone initiation (aOR 0.980, 95% CI (0.971 – 0.999).

Conclusions: Ceftriaxone 2 grams daily when used as appropriate antimicrobial coverage may be appropriate for ICU patients with lower mortality risk.

Background

Optimal concentrations of unbound antimicrobials are essential for maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model.

Methods

Design

Prospective, three phase intervention observational study.

Subjects

Healthy Merino sheep.

Interventions

Eight sheep were subject to three experimental phases; normoalbuminemia, hypoalbuminemia using plasmapheresis and albumin replacement using a 25% albumin solution. In each phase, ceftriaxone 40 mg/kg and ertapenem 15 mg/kg were given intravenously. Blood samples were collected at pre-defined intervals and analyzed using an ultra-high-performance liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters such as area under the curve (AUC_0-24), plasma clearance (CL) and apparent volume of distribution in the terminal phase (V_d) were estimated and compared between the phases.

Results

The protein and albumin concentrations were significantly different between phases. Hypoalbuminemia resulted in a significantly lower AUC_0-24 and higher CL of total and unbound concentrations of ceftriaxone compared to the other phases. Whereas albumin replacement led to higher AUC_0-24 and lower CL compared to other phases for both drugs. The V_d for total drug concentrations for both drugs were significantly lower with albumin replacement.

Conclusions

For highly protein-bound drugs such as ceftriaxone and ertapenem, both hypoalbuminemia and albumin replacement may affect unbound drug exposure.

Axonal protein synthesis has been shown to play a role in developmental and regenerative growth, as well as in the maintenance of the axoplasm in a steady state. Recent studies have begun to identify the mRNAs localized in axons, which could be translated locally under different conditions. Despite that by now hundreds or thousands of mRNAs have been shown to be localized into the axonal compartment of cultured neurons in vitro, knowledge of which mRNAs are localized in mature myelinated axons is quite limited. With the purpose of characterizing the transcriptome of mature myelinated motor axons of peripheral nervous systems, we modified the axon microdissection method devised by Koenig, enabling the isolation of the axoplasm RNA to perform RNA-seq analysis. The transcriptome analysis indicates that the number of RNAs detected in mature axons is lower in comparison with in vitro data, depleted of glial markers, and enriched in neuronal markers. The mature myelinated axons are enriched for mRNAs related to cytoskeleton, translation, and oxidative phosphorylation. Moreover, it was possible to define core genes present in axons when comparing our data with transcriptomic data of axons grown in different conditions. This work provides evidence that axon microdissection is a valuable method to obtain genome-wide data from mature and myelinated axons of the peripheral nervous system, and could be especially useful for the study of axonal involvement in neurodegenerative pathologies of motor neurons such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophies (SMA).

Sriram Sudarsanam, Shiri Yaniv, Hagar Meltzer, and Oren Schuldiner

The mechanisms that control intrinsic axon growth potential, and thus axon regeneration following injury, are not well understood. Developmental axon regrowth of Drosophila mushroom body -neurons during neuronal remodeling offers a unique opportunity to study the molecular mechanisms controlling intrinsic growth potential. Motivated by the recently uncovered developmental expression atlas of -neurons, we here focus on the role of the actin-severing protein cofilin during axon regrowth. We show that Twinstar (Tsr), the fly cofilin, is a crucial regulator of both axon growth and branching during developmental remodeling of -neurons. tsr mutant axons demonstrate growth defects both in vivo and in vitro, and also exhibit actin-rich filopodial-like structures at failed branch points in vivo. Our data is inconsistent with Tsr being important for increasing G-actin availability. Furthermore, analysis of microtubule localization suggests that Tsr is required for microtubule infiltration into the axon tips and branch points. Taken together, we show that Tsr promotes axon growth and branching, likely by clearing F-actin to facilitate protrusion of microtubules.

Viruses and mobile genetic elements are molecular parasites or symbionts that coevolve with nearly all forms of cellular life. The route of virus replication and protein expression is determined by the viral genome type. Comparison of these routes led to the classification of viruses into seven "Baltimore classes" (BCs) that define the major features of virus reproduction. However, recent phylogenomic studies identified multiple evolutionary connections among viruses within each of the BCs as well as between different classes. Due to the modular organization of virus genomes, these relationships defy simple representation as lines of descent but rather form complex networks. Phylogenetic analyses of virus hallmark genes combined with analyses of gene-sharing networks show that replication modules of five BCs (three classes of RNA viruses and two classes of reverse-transcribing viruses) evolved from a common ancestor that encoded an RNA-directed RNA polymerase or a reverse transcriptase. Bona fide viruses evolved from this ancestor on multiple, independent occasions via the recruitment of distinct cellular proteins as capsid subunits and other structural components of virions. The single-stranded DNA (ssDNA) viruses are a polyphyletic class, with different groups evolving by recombination between rolling-circle-replicating plasmids, which contributed the replication protein, and positive-sense RNA viruses, which contributed the capsid protein. The double-stranded DNA (dsDNA) viruses are distributed among several large monophyletic groups and arose via the combination of distinct structural modules with equally diverse replication modules. Phylogenomic analyses reveal the finer structure of evolutionary connections among RNA viruses and reverse-transcribing viruses, ssDNA viruses, and large subsets of dsDNA viruses. Taken together, these analyses allow us to outline the global organization of the virus world. Here, we describe the key aspects of this organization and propose a comprehensive hierarchical taxonomy of viruses.

Despite the importance of the Bering Sea for subarctic oceanography and climate, relatively little is known of the foraminifera from the extensive Aleutian Basin. We report the occurrence of modern deep-water agglutinated foraminifera collected at seven sites cored during Integrated Ocean Drilling Program (IODP) Expedition 323 in the Bering Sea. Assemblages collected from core-top samples contained 32 genera and 50 species and are described and illustrated here for the first time. Commonly occurring species include typical deep-water Rhizammina, Reophax, Rhabdammina, Recurvoides and Nodulina. Assemblages from the northern sites also consist of accessory Cyclammina, Eggerelloides and Glaphyrammina, whilst those of the Bowers Ridge sites consist of other tubular genera and Martinottiella. Of the studied stations with the lowest dissolved oxygen concentrations, the potentially Bering Sea endemic Eggerelloides sp. 1 inhabits the northern slope, which has the highest primary productivity, and the potentially endemic Martinottiella sp. 3 inhabits Bowers Ridge, which has the lowest oxygen concentrations but relatively low annual productivity. Martinottiella sp. 3, with open pores on its test surface, has previously been reported in Pliocene to Recent material from Bowers Ridge. Despite relatively small sample sizes, ecological constraints may imply that the Bering Sea experienced high productivity and reduced oxygen at times since at least the Pliocene. We note the partially endemic nature of the agglutinated foraminiferal assemblages, which may at least in part be due to basin restriction, the geologically long time period of reduced oxygen, and high organic carbon flux. Our results indicate the importance of gathering further surface sample data from the Aleutian Basin.

The Justice Department today announced settlements with two lenders under the Servicemembers Civil Relief Act (SCRA) to resolve allegations that the lenders wrongfully foreclosed upon active duty servicemembers without first obtaining court orders, in violation of the SCRA.

"The Civil Rights Division enforces several laws designed to protect the rights of members of the military – so that their brave and selfless service doesn’t put them at risk of losing their jobs at home; so that they don’t have to forfeit their right to vote; so that they can be assured they and their families in the consumer context will not be penalized for their courageous decision to serve our nation."

Temple University researchers discovered that boosting levels of a protein called Lin28 in injured spinal cords of mice prompts the regrowth of axons and repairs communication between the brain and body. They believe the discovery could be used to develop new treatments for both spinal cord and optic nerve injuries.

A microbiologist and an Anglo Saxon scholar decided to test a recipe from an Old English medical compendium called Bald's Leechbook, what they found surprised everyone.

Jamie Douglas Saxon was found guilty of murder in October after he stabbed Dominik Schulze, 30, during a Brisbane road-rage incident two years earlier.

Sacked 60 Minutes producer Stephen Rice has enlisted the help of a high-profile lawyer to fight his dismissal over the botched abduction of Sally Faulkner's two children in Lebanon last month.

Movie robots fall into one of three categories: the cutesy ones who do repairs (C3PO), the menacing bad guys designed to inflict pain (Mechagodzilla), and the child-like naifs who learn about the wonders and horrors of the world through experience. Angry Nerd explains why Neill Blomkamp’s new sci-fi flick “Chappie” falls into the third group and he breaks down why we need more movies that cast robots as the wide-eyed outsider.

Online Resource

With the release by the Office of Management and Budget of an updated Standard Occupational Classification (2018 SOC), the O*NET Program is moving forward with the transition to this new SOC standard. The technical report Updating the O*NET-SOC Taxonomy: Incorporating the 2018 SOC Structure describes the new O*NET-SOC 2019 taxonomy based on the 2018 SOC. The report summarizes code, title, and definition changes and the overall relationship between the 2018 SOC and the O*NET-SOC 2019 taxonomies.

To help with the transition to the new structure, related crosswalks are now available: Crosswalk O*NET-SOC 2019 to 2018 SOC, Crosswalk O*NET-SOC 2010 to O*NET-SOC 2019 and Crosswalk O*NET-SOC 2010 to 2018 SOC.

For more information, including an interactive summary graphic, a variety of occupational listings, and additional transition plans, visit O*NET Resource Center–O*NET-SOC Taxonomy.

With the release of the O*NET 25.1 Database in November 2020, O*NET Web Services will transition to the O*NET-SOC 2019 taxonomy. This taxonomy, based on the 2018 SOC, introduces several changes to the occupations returned by our services. It includes 1,016 occupational titles, 923 of which represent O*NET data-level occupations. For more information on these changes, see the O*NET-SOC Taxonomy page at the O*NET Resource Center.

To help O*NET Web Services users with the upcoming taxonomy transition, Taxonomy Services are now available to enable developers to connect occupational data between existing systems based on the O*NET-SOC 2010 taxonomy, and the future O*NET-SOC 2019 taxonomy-based O*NET Web Services.