Inflammasomes primarily restrict cytosolic replication within human macrophages.

serovar Typhimurium is a facultative intracellular pathogen that utilizes its type III secretion systems (T3SSs) to inject virulence factors into host cells and colonize the host. In turn, a subset of cytosolic immune receptors respond to T3SS ligands by forming multimeric signaling complexes called inflammasomes, which activate caspases that induce interleukin-1 (IL-1) family cytokine release and an inflammatory form of cell death called pyroptosis. Human macrophages mount a multifaceted inflammasome response to infection that ultimately restricts intracellular bacterial replication.

Detection of Viable Streptococcus equi equi Using Propidium Monoazide Polymerase Chain Reaction.

There is debate around the clinical significance of Streptococcus equi subsp. equi detection in low numbers using quantitative real-time PCR (qPCR). Propidium monoazide (PMA) qPCR has been used to differentiate DNA from viable and nonviable bacterial cells.

Replication Protein A1 is essential for DNA damage repair during mammalian oogenesis.

Persistence of unrepaired DNA damage in oocytes is detrimental and may cause genetic aberrations, miscarriage, and infertility. RPA, an ssDNA-binding complex, is essential for various DNA-related processes. Here we report that RPA plays a novel role in DNA damage repair during postnatal oocyte development after meiotic recombination.

Impaired dynamic X-chromosome inactivation maintenance in T cells is a feature of spontaneous murine SLE that is exacerbated in female-biased models.

Objective: Systemic lupus erythematosus (SLE) is a highly female-biased systemic autoimmune disease, but the molecular basis for this female bias remains incompletely elucidated. B and T lymphocytes from patients with SLE and female-biased mouse models of SLE exhibit features of epigenetic dysregulation on the X chromosome which may contribute to this strong female bias. We therefore examined the fidelity of dynamic X-chromosome inactivation maintenance (dXCIm) in the pathogenesis of two murine models of spontaneous lupus-NZM2328 and MRL/lpr-with disparate levels of female-bias to determine whether impaired dXCIm contributes to the female bias of disease.

Simultaneous Determination of Pyrethrins, Pyrethroids, and Piperonyl Butoxide in Animal Feeds by Liquid Chromatography-Tandem Mass Spectrometry.

The presence of insecticides like pyrethrins and synthetic pyrethroids, combined with the synergist piperonyl butoxide, in animal feeds can pose a risk to both animal and human health by contaminating the food chain. In this study, a simple and fast method was developed for the simultaneous determination of these compounds in contaminated animal feeds using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sample preparation was carried out using a QuEChERS-based approach, and the method was validated with acceptable accuracy ranging from 84 to 115% and precision below 10%.

The NDR/LATS protein kinases in neurobiology: Key regulators of cell proliferation, differentiation and migration in the ocular and central nervous system.

Nuclear Dbf2-related (NDR) kinases are a subgroup of evolutionarily conserved AGC protein kinases that regulate various aspects of cell growth and morphogenesis. There are 4 NDR protein kinases in mammals, LATS1, LATS2 and STTK8/NDR1, STK38L/NDR2 protein kinases. LATS1 and 2 are core components of the well-studied Hippo pathway, which play a critical role in the regulation of cell proliferation, differentiation, and cell migration via YAP/TAZ transcription factor.

TNF licenses macrophages to undergo rapid caspase-1, -11, and -8-mediated cell death that restricts Legionella pneumophila infection.

The inflammatory cytokine tumor necrosis factor (TNF) is necessary for host defense against many intracellular pathogens, including Legionella pneumophila. Legionella causes the severe pneumonia Legionnaires' disease and predominantly affects individuals with a suppressed immune system, including those receiving therapeutic TNF blockade to treat autoinflammatory disorders. TNF induces pro-inflammatory gene expression, cellular proliferation, and survival signals in certain contexts, but can also trigger programmed cell death in others.

Reconstitution of Human Prospermatogonial Development from Human-Induced Pluripotent Stem Cells.

There is a scarcity of information regarding the molecular mechanisms underlying human germ cell development due to limitations in obtaining the relevant materials. Reconstitution of human germ cell development from pluripotent stem cells in vitro would provide critical insight into the etiology of various reproductive conditions and disorders, including infertility.Recently, we reported the in vitro reconstitution of human prospermatogonial development from human-induced pluripotent stem cells through human primordial germ cell (PGC)-like cells (hPGCLCs) using long-term cultured xenogeneic reconstituted testes.

In Vitro and In Vivo Evaluation of Ultrasound-Triggered Release From Novel Spinal Device.

Objectives: Bacterial infection following spinal fusion is a major clinical concern with up to 20% incidence. An ultrasound-triggered bulk-release system to combat postsurgical bacterial survival was designed and evaluated.

Methods: Polylactic acid (PLA) clips were loaded with vancomycin (VAN) and microbubbles (Sonazoid, GE HealthCare) in vitro.

Evaluation of mechlorethamine, vinblastine, procarbazine, and prednisone for the treatment of resistant multicentric canine lymphoma.

Multi-agent chemotherapy successfully induces remission in most naïve, high-grade canine lymphoma patients; however, disease recurrence is common. MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) is an effective rescue protocol used to re-induce remission, but is associated with gastrointestinal toxicity and can be a less desirable option for patients that previously failed vincristine-containing protocols. Therefore, alternative members of the vinca alkaloid family, such as vinblastine, could be potentially advantageous as substitutes for vincristine to reduce gastrointestinal toxicity and chemoresistance.

Dapagliflozin prevents abdominal visceral and subcutaneous adipose tissue dysfunction in the insulin-resistant canine model.

Objective: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) promote urinary glucose excretion, induce weight loss, and reduce fat accumulation. The effects of the SGLT2i dapagliflozin (DAPA) on subcutaneous (SC) and visceral (VIS) adipose tissue function remain unclear. The objective of this study is to evaluate SC and VIS adipose tissue function in an insulin-resistant canine model.

Effect of testicular degeneration on expression of sperm protein at 22 kDa in stallions.

Background: Sperm protein at 22 kDa has been associated with fertility.

Objectives: The objectives of this study were to determine (1) the localization pattern of SP22 on ejaculated and caudal epididymal equine spermatozoa and in epididymal fluid, and to (2) characterize SP22 protein and mRNA expression in testicular and epididymal tissues in response to heat-induced testicular degeneration.

Materials And Methods: Semen was collected before and after hemi-castration, as well as prior to and following insulation of the remaining testes, and tissue specimens were collected for analysis.

TLR priming licenses NAIP inflammasome activation by immunoevasive ligands.

NLR family, apoptosis inhibitory proteins (NAIPs) detect bacterial flagellin and structurally related components of bacterial type III secretion systems (T3SS), and recruit NLR family, CARD domain containing protein 4 (NLRC4) and caspase-1 into an inflammasome complex that induces pyroptosis. NAIP/NLRC4 inflammasome assembly is initiated by the binding of a single NAIP to its cognate ligand, but a subset of bacterial flagellins or T3SS structural proteins are thought to evade NAIP/NLRC4 inflammasome sensing by not binding to their cognate NAIPs. Unlike other inflammasome components such as NLRP3, AIM2, or some NAIPs, NLRC4 is constitutively present in resting macrophages, and not thought to be regulated by inflammatory signals.

Developmental origins of mammalian spermatogonial stem cells: New perspectives on epigenetic regulation and sex chromosome function.

Male and female germ cells undergo genome-wide reprogramming during their development, and execute sex-specific programs to complete meiosis and successfully generate healthy gametes. While sexually dimorphic germ cell development is fundamental, similarities and differences exist in the basic processes governing normal gametogenesis. At the simplest level, male gamete generation in mammals is centred on the activity of spermatogonial stem cells (SSCs), and an equivalent cell state is not present in females.

Numerical analysis of the mechanical response of novel swelling bone implants in polyurethane foams.

In this study, a numerical framework was developed in order to analyze the swelling properties, mechanical response and fixation strength of swelling bone anchors. Using this framework, fully porous and solid implants, along with a novel hybrid design (consisting of a solid core and a porous sleeve), were modeled and studied. Free swelling experiments were conducted to investigate their swelling characteristics.

The MOV10 RNA helicase is a dosage-dependent host restriction factor for LINE1 retrotransposition in mice.

Transposable elements constitute nearly half of the mammalian genome and play important roles in genome evolution. While a multitude of both transcriptional and post-transcriptional mechanisms exist to silence transposable elements, control of transposition in vivo remains poorly understood. MOV10, an RNA helicase, is an inhibitor of mobilization of retrotransposons and retroviruses in cell culture assays.

Flow-controlled expiration reduces positive end-expiratory pressure requirement in dorsally recumbent, anesthetized horses.

Introduction: Equine peri-anesthetic mortality is higher than that for other commonly anesthetized veterinary species. Unique equine pulmonary pathophysiologic aspects are believed to contribute to this mortality due to impairment of gas exchange and subsequent hypoxemia. No consistently reliable solution for the treatment of peri-anesthetic gas exchange impairment is available.

Subarachnoid hemorrhage and axonal degeneration after C1-C2 cervical centesis in 2 horses.

Ultrasound-guided cervical centesis has gained popularity as a method for collecting cerebrospinal fluid (CSF) from standing horses. There are anecdotal reports of neck stiffness, regional swelling, sensitivity to palpation, and fever after the procedure. We report 2 horses with complications that occurred within days of C1-C2 centesis and ultimately resulted in euthanasia.

The DOT1L-MLLT10 complex regulates male fertility and promotes histone removal during spermiogenesis.

Histone modifications regulate chromatin remodeling and gene expression in development and diseases. DOT1L, the sole histone H3K79 methyltransferase, is essential for embryonic development. Here, we report that DOT1L regulates male fertility in mouse.

Resolution of paraneoplastic hypoglycemia following nephroureterectomy for treatment of canine renal cell carcinoma: Case report.

Objectives: To describe the clinicopathologic findings, imaging results, surgical treatment, and outcome of a dog with renal cell carcinoma (RCC) and paraneoplastic hypoglycemia.

Animals: A 13-year-old female spayed mixed breed dog that was presented for facial twitching and neurologic decline and diagnosed with a renal mass and paraneoplastic hypoglycemia.

Study Design: Case report.

Arresting microbiome development limits immune system maturation and resistance to infection in mice.

Disruptions to the intestinal microbiome during weaning lead to negative effects on host immune function. However, the critical host-microbe interactions during weaning that are required for immune system development remain poorly understood. We find that restricting microbiome maturation during weaning stunts immune system development and increases susceptibility to enteric infection.

Calculation of dose intensity and comparison of published methods using a cohort of canine T-cell lymphoma patients undergoing CHOP-based chemotherapy.

Methods of calculating and reporting dose intensity (DI) of CHOP-based protocols in the veterinary literature vary. The goal of this retrospective study is to examine the prognostic significance of the average percentage of planned DI received in a cohort of canine T-cell lymphoma patients treated with a modified CHOP protocol with corresponding toxicity and efficacy data. Our data set of 40 dogs was analysed using various previously published methods for calculating DI.

How Triceratops got its face: An update on the functional evolution of the ceratopsian head.

Ceratopsian dinosaurs arguably show some of the most extravagant external cranial morphology across all Dinosauria. For over a century, ceratopsian dinosaurs have inspired a multitude of cranial functional studies as more discoveries continued to depict a larger picture of the enormous diversity of these animals. The iconic horns and bony frills in many ceratopsians portray a plethora of shapes, sizes, and arrangements across taxa, and their overall feeding apparatus show the development of unique specializations previously unseen in large herbivores.