Lineage labeling with zebrafish Cre and CreERT2 recombinase CRISPR knock-ins.

Background: The ability to generate endogenous Cre recombinase drivers using CRISPR-Cas9 knock-in technology allows lineage tracing, cell type specific gene studies, and validation of inferred developmental trajectories from phenotypic and gene expression analyses. This report describes endogenous zebrafish Cre and CreERT2 drivers generated with GeneWeld CRISPR-Cas9 precision targeted integration.

Results: and knock-ins crossed with ubiquitous -based Switch reporters led to broad labeling in expected mesodermal and neural crest-derived lineages in cardiac, pectoral fins, pharyngeal arch, liver, intestine, and mesothelial tissues, as well as enteric neurons.

Deformable Capsules for Object Detection.

Capsule networks promise significant benefits over convolutional networks by storing stronger internal representations, and routing information based on the agreement between intermediate representations' projections. Despite this, their success has been limited to small-scale classification datasets due to their computationally expensive nature. Though memory efficient, convolutional capsules impose geometric constraints that fundamentally limit the ability of capsules to model the pose/deformation of objects.

How debunking biases in research and development decisions could lead to more equitable healthcare?

Decades of research have demonstrated that a variety of cognitive biases can affect our judgment and ability to make rational decisions in personal and professional environments. The lengthy, risky, and costly nature of pharmaceutical research and development (R&D) makes it vulnerable to biased decision-making. Moreover, cognitive biases can play a role in regulatory and clinical decision-making, the latter impacting diagnostic and treatment decisions in the therapeutic use of medicines.

: Safe harbor landing sites for reproducible and efficient transgenesis in zebrafish.

Standard zebrafish transgenesis involves random transgene integration with resource-intensive screening. While phiC31 integrase-based / recombination has streamlined transgenesis in mice and , validated -based landing sites for universal applications are lacking in zebrafish. Here, we developed () as transgenesis approach, with two landing sites and from well-validated Tol2 transgenes.

Neurochemical Anatomy of Cushing's Syndrome.

The neurochemical anatomy underlying Cushing's syndrome is examined for regional brain metabolism as well as neurotransmitter levels and receptor binding of biogenic amines and amino acids. Preliminary studies generally indicate that glucose uptake, blood flow, and activation on fMRI scans decreased in neocortical areas and increased in subcortical areas of patients with Cushing's syndrome or disease. Glucocorticoid-mediated increases in hippocampal metabolism occurred despite in vitro evidence of glucocorticoid-induced decreases in glucose uptake or consumption, indicating that in vivo increases are the result of indirect, compensatory, or preliminary responses.

The neuropharmacological profile of interval responding during operant tasks.

Responses occurring during intervals of operant tasks have been subdivided as interim, facultative, and terminal, depending on the time between response onset and reward. Although interval responses, also known as adjunctive responses, have been described in pigeons, rats, mice, monkeys, and humans, most experiments have been conducted in rats. We review the neurochemical basis of interval responses and examine the hypothesis that these responses modulate operant performance.

Anxiolytic-like effects of milk proteins.

Milk varieties and specific proteins exhibit anxiolytic-like actions in mice and rats exposed to several tests, the most prominent being the elevated plus-maze. Administrations of α-casein, its 91-100 (α-casozepine), 91-97, 91-93, and 91-92 fragments, the 60-69 fragment of β-casein, lactoferrin, β-lactotensin, wheylin-1, wheylin-2, and α-lactalbumin have been reported to increase open arm exploration relative to enclosed arm exploration. Anxiolytic-like actions have also been described for 91-93 and 91-92 fragments of α-casein, wheylin-1, α-lactalbumin, and lactoferrin in the open-field.

Tree adaptive growth (TAG) model: a life-history theory-based analytical model for post-thinning forest stand dynamics.

Background: Understanding stand dynamics is essential for predicting future wood supply and associated ecosystem services for sustainable forest management. The dynamics of natural stands can be characterized by age-dependent growth and yield models. However, dynamics in managed stands appear somewhat different from that of natural stands, especially with difficulties in explaining the phenomenon of post-thinning overcompensation, based upon some long-term observations.

The gene in neurobiology.

is a gene whose alternative splicing yields epithelial, neuronal, and muscular isoforms. The autosomal recessive () spontaneous mouse mutation causes degeneration of spinocerebellar tracts as well as peripheral sensory nerves, dorsal root ganglia, and cranial nerve ganglia. In addition to mutants, axonopathy and neurofilament accumulation in perikarya are features of two other murine lines with spontaneous mutations, targeted knockout mice, Tg4 transgenic mice carrying two deleted exons, mice with trapped actin-binding domain-containing isoforms, and conditional Schwann cell-specific knockout mice.

: Safe harbor landing sites for reproducible and efficient transgenesis in zebrafish.

Standard methods for transgenesis in zebrafish depend on random transgene integration into the genome followed by resource-intensive screening and validation. Targeted vector integration into validated genomic loci using phiC31 integrase-based / recombination has transformed mouse and transgenesis. However, while the phiC31 system functions in zebrafish, validated loci carrying -based landing or safe harbor sites suitable for universal transgenesis applications in zebrafish have not been established.

Single isocenter HyperArc treatment of multiple intracranial metastases: Targeting accuracy.

Purpose/objectives: (A) To examine the alignment accuracy of CBCT guidance for brain metastases with off centered isocenters, (B) to test dose delivery and targeting accuracy for single isocenter treatments with multiple brain metastases. We report the results of the end-to-end test for Truebeam stereotactic radiosurgery (SRS).

Materials/methods: An anthropomorphic CT head phantom was drilled with five MOSFET inserts and two PTW Pinpoint chamber inserts.

Corticosterone effects on postnatal cerebellar development in mice.

Glucocorticoids administered early in infancy can affect the architectonic organization of brain structures, particularly those with a postnatal development and resulting in long-term deficits of neuromotor function and cognition. The present study was undertaken to study the effects of daily corticosterone (CORT) injections at a pharmacological dose from postnatal days 8-15 on cerebellar and hippocampal development in mouse pups. Gene expression status for trophic factors involved in synaptic development and function as well as measures of layer thickness associated with cytochrome oxidase labelling were analyzed in the hippocampus, hypothalamus, and specific cerebellar lobules involved in motor control.

BDNF and Cerebellar Ataxia.

Brain-derived neurotrophic factor (BDNF) has been proposed as a treatment for neurodegeneration, including diseases of the cerebellum, where BDNF levels or those of its main receptor, TrkB, are often diminished relative to controls, thereby serving as replacement therapy. Experimental evidence indicates that BDNF signaling countered cerebellar degeneration, sensorimotor deficits, or both, in transgenic mice mutated for ataxin-1, Cacna1a knock-in mice mutated for ataxin-6, mice injected with lentivectors encoding RNA sequences against human FXN into the cerebellar cortex, mutant mice with granule cell degeneration, and rats with olivocerebellar transaction, similar to a -overexpressing transgenic line interbred with mutant mice. In this regard, this study discusses whether BDNF is effective in cerebellar pathologies where BDNF levels are normal and whether it is effective in cases with combined cerebellar and basal ganglia damage.

Probiotic Influences on Motor Skills: A Review.

The effects of probiotics have mostly been shown to be favorable on measures of anxiety and stress. More recent experiments indicate single- and multi-strain probiotics in treating motorrelated diseases. Initial studies in patients with Parkinson's disease and Prader-Willi syndrome are concordant with this hypothesis.

The Neuroanatomical Basis of the 5-HT Syndrome and Harmalineinduced Tremor.

The 5-HT syndrome in rats is composed of head weaving, body shaking, forepaw treading, flat body posture, hindlimb abduction, and Straub tail. The importance of the brainstem and spinal cord for the syndrome is underlined by findings of 5,7-dihydroxytryptamine (5,7-DHT)-induced denervation supersensitivity in response to 5-HT-stimulant drugs. For head weaving and Straub tail, supersensitivity occurred when the neurotoxin was injected into the cisterna magna or spinal cord, for forepaw treading in cisterna magna, and for hindlimb abduction in the spinal cord.

One-Trial Appetitive Learning Tasks for Drug Targeting.

One-trial appetitive learning developed from one-trial passive avoidance learning as a standard test of retrograde amnesia. It consists of one learning trial followed by a retention test, in which physiological manipulations are presented. As in passive avoidance learning, food- or waterdeprived rats or mice finding food or water inside an enclosure are vulnerable to the retrograde amnesia produced by electroconvulsive shock treatment or the injection of various drugs.

A median fin derived from the lateral plate mesoderm and the origin of paired fins.

The development of paired appendages was a key innovation during evolution and facilitated the aquatic to terrestrial transition of vertebrates. Largely derived from the lateral plate mesoderm (LPM), one hypothesis for the evolution of paired fins invokes derivation from unpaired median fins via a pair of lateral fin folds located between pectoral and pelvic fin territories. Whilst unpaired and paired fins exhibit similar structural and molecular characteristics, no definitive evidence exists for paired lateral fin folds in larvae or adults of any extant or extinct species.

Lateral thinking in syndromic congenital cardiovascular disease.

Syndromic birth defects are rare diseases that can present with seemingly pleiotropic comorbidities. Prime examples are rare congenital heart and cardiovascular anomalies that can be accompanied by forelimb defects, kidney disorders and more. Whether such multi-organ defects share a developmental link remains a key question with relevance to the diagnosis, therapeutic intervention and long-term care of affected patients.

A novel approach to infectious disease control and radiotherapy risk management.

Background: Infectious disease outbreaks have always presented challenges to the operation of healthcare systems. In particular, the treatment of cancer patients within Radiation Oncology often cannot be delayed or compromised due to infection control measures. Therefore, there is a need for a strategic approach to simultaneously managing infection control and radiotherapy risks.

Functional comparison of human ACVR1 and zebrafish Acvr1l FOP-associated variants in embryonic zebrafish.

Background: Fibrodysplasia ossificans progressiva (FOP), a rare disease characterized by progressive heterotopic ossification of muscle and connective tissues, is caused by autosomal dominant activating mutations in the type I receptor, ACVR1/ALK2. The classic human FOP variant, ACVR1 , shows increased bone morphogenetic protein (BMP) signaling and activation by activins.

Results: Here, we performed in vivo functional characterization of human ACVR1 and orthologous zebrafish Acvr1l using early embryonic zebrafish dorsoventral patterning as a phenotypic readout for receptor activity.

Modelling the stand dynamics after a thinning induced partial mortality: A compensatory growth perspective.

Introduction: With increasing forest areas under management, dynamics of managed stands have gained more attention by forest managers and practitioners. Improved understanding on how trees and forest stands would respond to different disturbances is required to predict the dynamics of managed stand.s.

Neurobehavioral basis of Maier 3-table and other matching-to-place tasks.

The Maier 3-table task comprises three phases conducted each day. During the exploration phase, rats explore the entire apparatus. During the information phase, the rats are placed on one of the three tables where food is found.

Functional Testing of Bone Morphogenetic Protein (BMP) Pathway Variants Identified on Whole-Exome Sequencing in a Patient with Delayed-Onset Fibrodysplasia Ossificans Progressiva (FOP) Using ACVR1 -Specific Human Cellular and Zebrafish Models.

Bone morphogenetic protein (BMP) signaling is critical in skeletal development. Overactivation can trigger heterotopic ossification (HO) as in fibrodysplasia ossificans progressiva (FOP), a rare, progressive disease of massive HO formation. A small subset of FOP patients harboring the causative ACVR1 mutation show strikingly mild or delayed-onset HO, suggesting that genetic variants in the BMP pathway could act as disease modifiers.