Is bovine somatotropin an alternative strategy to overcome the detrimental effects of high-gain diets on prepubertal Holstein × Gyr heifers?

Feeding high-gain diets and an inadequate energy and protein ratio during pre-puberty may lead to impaired growth and mammary gland development of heifers. Thus, frequent application of bovine somatotropin (bST) may prevent future losses in productivity, improve mammary development and animal performance. We aimed to evaluate the effects of bST on digestibility, performance, blood metabolites, mammary gland development, and carcass composition of high-performance prepubertal Holstein × Gyr heifers. Thirty-four Holstein × Gyr heifers with an average initial body weight of 218 ± 49 kg and 14 ± 4 months of age were submitted to an 84-day trial evaluating the effects of no bST or bST injections. Treatments were randomly assigned to each animal within one of the tree blocks. The bST did not influence digestibility or performance parameters. Regarding blood results, IGF1 concentration presented an interaction between treatment and day, where bST heifers had the highest IGF1 concentration. Heifers receiving bST also showed increased ribeye area; however, only an experimental day effect for backfat thickness was observed, with greater accumulation of carcass fat on day 84. Heifers receiving bST had lower pixels/mm² on parenchyma, characteristic of greater parenchymal tissue. Moreover, heifers on bST treatment also had reduced pixels/mm2, characteristic of reduced fat pad tissue. Lastly, bST injections did not influence liver and muscle gene expression, nor most genes evaluated in mammary gland tissue, except for IGFBP3 expression, which was greater for bST heifers. In summary, we confirm the efficacy of bST injections to overcome the detrimental effects of high-gain diets on mammary gland growth and to improve lean carcass gain of prepubertal Holstein × Gyr heifers.

Effect of protein supplement level on the productive and reproductive parameters of replacement heifers managed in intensive grazing systems.

Evaluations of replacement heifers in intensively managed grazing systems in tropical conditions are warranted. Thus, we aimed to evaluate performance, muscle and mammary gland development, oocyte quality, and in vitro production of embryos of crossbred heifers grazing an intensively managed pasture and supplemented with high or low protein concentrates. Eighteen pubertal crossbred heifers (Holstein x Gyr) with an initial weight of 350 ± 8.0 kg were used in a 60-day trial. Two supplement types, 12% crude protein (CP) (S12CP) or 24% CP (S24CP), and a control treatment (mineral mixture, CON) were randomly distributed to the heifers. Throughout the experiment, four digestibility trials were performed over four consecutive days. Four ovarium pick-ups were performed to evaluate oocyte quality and in vitro embryo production. Lastly, ultrasounds of carcasses and mammary glands were performed. The intakes of dry matter (DM), digestible energy (DE), and CP were greater for supplemented (SUP) compared with CON heifers. The SUP heifers had a greater average daily gain (ADG) (645 versus 390 g/d) and rib eye area (58.78 versus 53.32 cm2) than the CON heifers. Oocyte recovery, quality, and follicle features were not affected by supplementation strategy. However, the cleavage rate (47.17% versus 30.31%) and blastocyst rate (27.91% versus 10.12%) were negatively affected by supplementation. The S12CP presented a blastocyst rate much lower than the S24CP (3.02% versus 17.23%). Carcass ultrasonography indicated a trend for greater rib eye area for S24CP and mammary ultrasonography indicated no effects of supplementation on mammary gland development. In summary, supplementation seems to be an appropriate strategy for satisfactory performance, with greater muscle deposition and no negative impacts on mammary gland development. However, in vitro embryo production was impaired when the animals received the supplementation with 12% CP.

Cone-Beam Computed Tomography Incidental Findings in Individuals With Cleft Lip and Palate.

OBJECTIVES: The use of cone-beam computed tomography (CBCT) is well-established in clinical practice. This study seeks to categorize and quantify the incidental finding (IF) rate on CBCT in patients with cleft lip and palate (CLP) prior to orthodontic or surgical treatment. METHODS: This is systematic retrospective review of head and neck CBCTs in patients with nonsyndromic CLP taken between 2012 and 2019 at a single tertiary referral center. All assessments were performed independently by 4 observers (a head and neck radiologist and 3 orthodontists, including 2 fellowship-trained cleft-craniofacial orthodontists ). The images were divided into 9 anatomical areas and screened using serial axial slices and 3D reconstructions. The absolute number of IFs was reported for each area and statistical analysis was performed. RESULTS: Incidental findings were found in 106 (95.5%) of the 111 patients. The most common sites were the maxilla (87.4%, principally dental anomalies), paranasal sinuses (46.8%, principally inflammatory opacification), and inner ear cavities (18.9%, principally inflammatory opacification). Eleven patients had skull malformations. Thirty-three patients had IFs in 1 anatomical area, 49 patients in 2 anatomical areas, 19 patients in 3 areas, and 5 patients presented with IFs in 4 of the 9 anatomical areas. DISCUSSION: In patients with CLP, IFs on CBCT exam were present in the majority of cases. Most patients with IFs had them in multiple anatomical areas of the head and neck. The maxillary dental-alveolar complex was the most common area. Inflammatory changes in the inner ear cavities and paranasal sinuses were also common; however, cervical spine and skull abnormalities were also identified. Clinicians caring for patients with CLP should be aware of IFs, which may warrant further investigation and treatment.

CXCL4 assembles DNA into liquid crystalline complexes to amplify TLR9-mediated interferon-α production in systemic sclerosis.

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis and vasculopathy. CXCL4 represents an early serum biomarker of severe SSc and likely contributes to inflammation via chemokine signaling pathways, but the exact role of CXCL4 in SSc pathogenesis is unclear. Here, we elucidate an unanticipated mechanism for CXCL4-mediated immune amplification in SSc, in which CXCL4 organizes "self" and microbial DNA into liquid crystalline immune complexes that amplify TLR9-mediated plasmacytoid dendritic cell (pDC)-hyperactivation and interferon-α production. Surprisingly, this activity does not require CXCR3, the CXCL4 receptor. Importantly, we find that CXCL4-DNA complexes are present in vivo and correlate with type I interferon (IFN-I) in SSc blood, and that CXCL4-positive skin pDCs coexpress IFN-I-related genes. Thus, we establish a direct link between CXCL4 overexpression and the IFN-I-gene signature in SSc and outline a paradigm in which chemokines can drastically modulate innate immune receptors without being direct agonists.

Externalized histone H4 orchestrates chronic inflammation by inducing lytic cell death.

The perpetuation of inflammation is an important pathophysiological contributor to the global medical burden. Chronic inflammation is promoted by non-programmed cell death1,2; however, how inflammation is instigated, its cellular and molecular mediators, and its therapeutic value are poorly defined. Here we use mouse models of atherosclerosis-a major underlying cause of mortality worldwide-to demonstrate that extracellular histone H4-mediated membrane lysis of smooth muscle cells (SMCs) triggers arterial tissue damage and inflammation. We show that activated lesional SMCs attract neutrophils, triggering the ejection of neutrophil extracellular traps that contain nuclear proteins. Among them, histone H4 binds to and lyses SMCs, leading to the destabilization of plaques; conversely, the neutralization of histone H4 prevents cell death of SMCs and stabilizes atherosclerotic lesions. Our data identify a form of cell death found at the core of chronic vascular disease that is instigated by leukocytes and can be targeted therapeutically.

Evolution of Cell Size Homeostasis and Growth Rate Diversity during Initial Surface Colonization of Shewanella oneidensis.

Cell size control and homeostasis are fundamental features of bacterial metabolism. Recent work suggests that cells add a constant size between birth and division ("adder" model). However, it is not known how cell size homeostasis is influenced by the existence of heterogeneous microenvironments, such as those during biofilm formation. Shewanella oneidensis MR-1 can use diverse energy sources on a range of surfaces via extracellular electron transport (EET), which can impact growth, metabolism, and size diversity. Here, we track bacterial surface communities at single-cell resolution to show that not only do bacterial motility appendages influence the transition from two- to three-dimensional biofilm growth and control postdivisional cell fates, they strongly impact cell size homeostasis. For every generation, we find that the average growth rate for cells that stay on the surface and continue to divide (nondetaching population) and that for cells that detach before their next division (detaching population) are roughly constant. However, the growth rate distribution is narrow for the nondetaching population, but broad for the detaching population in each generation. Interestingly, the appendage deletion mutants (ΔpilA, ΔmshA-D, Δflg) have significantly broader growth rate distributions than that of the wild type for both detaching and nondetaching populations, which suggests that Shewanella appendages are important for sensing and integrating environmental inputs that contribute to size homeostasis. Moreover, our results suggest multiplexing of appendages for sensing and motility functions contributes to cell size dysregulation. These results can potentially provide a framework for generating metabolic diversity in S. oneidensis populations to optimize EET in heterogeneous environments.