Quantitative analysis of drug distribution by ambient mass spectrometry imaging method with signal extinction normalization strategy and inkjet-printing technology

Publication date: 1 March 2018
Source:Talanta, Volume 179
Author(s): Zhigang Luo, Jingjing He, Jiuming He, Lan Huang, Xiaowei Song, Xin Li, Zeper Abliz
Quantitative mass spectrometry imaging (MSI) is a robust approach that provides both quantitative and spatial information for drug candidates' research. However, because of complicated signal suppression and interference, acquiring accurate quantitative information from MSI data remains a challenge, especially for whole-body tissue sample. Ambient MSI techniques using spray-based ionization appear to be ideal for pharmaceutical quantitative MSI analysis. However, it is more challenging, as it involves almost no sample preparation and is more susceptible to ion suppression/enhancement. Herein, based on our developed air flow-assisted desorption electrospray ionization (AFADESI)-MSI technology, an ambient quantitative MSI method was introduced by integrating inkjet-printing technology with normalization of the signal extinction coefficient (SEC) using the target compound itself. The method utilized a single calibration curve to quantify multiple tissue types. Basic blue 7 and an antitumor drug candidate (S-(+)-deoxytylophorinidine, CAT) were chosen to initially validate the feasibility and reliability of the quantitative MSI method. Rat tissue sections (heart, kidney, and brain) administered with CAT was then analyzed. The quantitative MSI analysis results were cross-validated by LC-MS/MS analysis data of the same tissues. The consistency suggests that the approach is able to fast obtain the quantitative MSI data without introducing interference into the in-situ environment of the tissue sample, and is potential to provide a high-throughput, economical and reliable approach for drug discovery and development.

Graphical abstract

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Pleomorphic mastocytoma in an adult

A cutaneous mastocytoma (CM) is a clinical variant of cutaneous mastocytosis. It is defined as the presence of up to 3 isolated mast cell skin lesions. When only 1 lesion is observed, the patient is classified as having a solitary mastocytoma, and when 4 or more lesions are observed, the patient should be classified as having urticaria pigmentosa (1).

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Scholar : Environmental Forensics, Volume 18, Issue 4, October 2, 2017 is now available online on Taylor & Francis Online

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The online platform for Taylor & Francis Online content Environmental Forensics, Volume 18, Issue 4, October 2, 2017 is now available online on Taylor & Francis Online. This new issue contains the following articles: Scientific Communication Distribution and potential ecological risk of heavy metals accumulated in subsidence lakes formed in the Huainan Coalfield, China Yunhu Hu, Zhongbing Dong & Guijian Liu Pages: 251-257 | DOI: 10.1080/15275922.2017.1368040 Contributed Articles AETC: Segmentation and classification of the oil spills from SAR imagery J. Senthil Murugan & V. Parthasarathy Pages: 258-271 | DOI: 10.1080/15275922.2017.1368044 Determining groundwater MTBE sources using reverse particle tracking: Two case studies Farrukh Mohsen & Randy O'Boyle Pages: 272-284 | DOI: 10.1080/15275922.2017.1368043 Reassessment of dibenzothiophene as marker for petroleum and coal contamination in sediments from Imo River, SE Nigeria Orok E. Oyo-Ita, Inyang O. Oyo-Ita & Soumaya Elarboui Pages: 285-295 | DOI: 10.1080/15275922.2017.1368045 Impact of pit latrines on drinking water contaminations in Khyber Pakhtunkhwa, Pakistan Bahadar Nawab, Kjell B. Esser & Shams Ali Baig Pages: 296-306 | DOI: 10.1080/15275922.2017.1368042 Modeling the formation of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the historical manufacture of 2,4,5-trichlorophenol Robert Parette, Robert McCrindle, Katherine S. McMahon, Valerie J. Watson, Michael J. Janik, Darrell Velegol, Frank L. Dorman & Wendy N. Pearson Pages: 307-317 | DOI: 10.1080/15275922.2017.1368047 Trace element analysis and associated risk assessment in mining area soils from Zhexi river plain, Zhejiang, China Ying Wang, Wenbo Yan, Hua Guo, Qaisar Mahmood, Jia Guo, Chen Liu, Bin Zhong & Dan Liu Pages: 318-330 | DOI: 10.1080/15275922.2017.1368046 Radioactivity level of dug well water across selected cities in two states of Nigeria A. E. Ayodele, A. M. Arogunjo, J. I. Ajisafe & O. T. Arije Pages: 331-338 | DOI: 10.1080/15275922.2017.1368041 Editorial Board Editorial Board EOV Pages: ebi-ebi | DOI: 10.1080/15275922.2017.1380476 Free access to articles in this Editor's Choice collection from the Journal of Control and Decision. Don't miss it! To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

The microbiota protects against respiratory infection via GM-CSF signaling.

The microbiota protects against respiratory infection via GM-CSF signaling.

Nat Commun. 2017 Nov 15;8(1):1512

Authors: Brown RL, Sequeira RP, Clarke TB

Abstract
The microbiota promotes resistance to respiratory infection, but the mechanistic basis for this is poorly defined. Here, we identify members of the microbiota that protect against respiratory infection by the major human pathogens Streptococcus pneumoniae and Klebsiella pneumoniae. We show that the microbiota enhances respiratory defenses via granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which stimulates pathogen killing and clearance by alveolar macrophages through extracellular signal-regulated kinase signaling. Increased pulmonary GM-CSF production in response to infection is primed by the microbiota through interleukin-17A. By combining models of commensal colonization in antibiotic-treated and germ-free mice, using cultured commensals from the Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria phyla, we found that potent Nod-like receptor-stimulating bacteria in the upper airway (Staphylococcus aureus and Staphylococcus epidermidis) and intestinal microbiota (Lactobacillus reuteri, Enterococcus faecalis, Lactobacillus crispatus and Clostridium orbiscindens) promote resistance to lung infection through Nod2 and GM-CSF. Our data reveal the identity, location, and properties of bacteria within the microbiota that regulate lung immunity, and delineate the host signaling axis they activate to protect against respiratory infection.

PMID: 29142211 [PubMed - in process]

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Scholar : These new articles for Classroom Discourse are available online

The online platform for Taylor & Francis Online content New for Classroom Discourse and online now on Taylor & Francis Online: Original Articles Clarifications and carnival: Children's embodied investments in a literacy conversation Helle Pia Laursen & Kirsten L. Kolstrup Pages: 1-20 | DOI: 10.1080/19463014.2017.1392880 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

New excavations at the HWK EE site: Archaeology, paleoenvironment and site formation processes during late Oldowan times at Olduvai Gorge, Tanzania

Publication date: Available online 15 November 2017
Source:Journal of Human Evolution
Author(s): Ignacio de la Torre, Rosa M. Albert, Adrián Arroyo, Richard Macphail, Lindsay J. McHenry, Rafael Mora, Jackson K. Njau, Michael C. Pante, Carlos A. Rivera-Rondón, Ágata Rodríguez-Cintas, Ian G. Stanistreet, Harald Stollhofen, Karol Wehr
This paper reports the results of renewed fieldwork at the HWK EE site (Olduvai Gorge, Tanzania). HWK EE is positioned across the boundary between Lower and Middle Bed II, a crucial interval for studying the emergence of the Acheulean at Olduvai Gorge. Our excavations at HWK EE have produced one of the largest collections of fossils and artefacts from any Oldowan site, distributed across several archaeological units and a large excavation surface in four separate trenches that can be stratigraphically correlated. Here we present the main stratigraphic and archaeological units and discuss site formation processes. Results show a great density of fossils and stone tools vertically through two stratigraphic intervals (Lemuta and Lower Augitic Sandstone) and laterally across an area of around 300 m², and highlight the confluence of biotic and abiotic agents in the formation of the assemblage. The large size and diversity of the assemblage, as well as its good preservation, qualify HWK EE as a reference site for the study of the late Oldowan at Olduvai Gorge and elsewhere in Africa. In addition, the description of the stratigraphic and archaeological sequence of HWK EE presented in this paper constitutes the foundation for further studies on hominin behavior and paleoecology in Lower and Middle Bed II.



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Scholar : These new articles for Contemporary Theatre Review are available online

@media screen and (max-width:400px) { .two .column, .two .left, .two .right{ max-width: 100% !important; } } @media screen and (min-width: 401px) and (max-width:620px){ .two .column, .two .left, .two .right { max-width: 100% !important; } }

The online platform for Taylor & Francis Online content New for Contemporary Theatre Review and online now on Taylor & Francis Online: Documents Performing Memory, Challenging History: Two Adaptations of The Unknown Soldier | Julia Pajunen & Hanna Korsberg Pages: 1-11 | DOI: 10.1080/10486801.2017.1365715 Routledge Performance Archive - http://ift.tt/1txaJgs "Take a Tour" to find out more and recommend the Archive to your librarian to arrange a free trial for your institution. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

When syntax meets action: Brain potential evidence of overlapping between language and motor sequencing

Publication date: Available online 15 November 2017
Source:Cortex
Author(s): Pilar Casado, Manuel Martín-Loeches, Inmaculada León, David Hernández-Gutiérrez, Javier Espuny, Francisco Muñoz, Laura Jiménez-Ortega, Sabela Fondevila, Manuel de Vega
This study aims to extend the embodied cognition approach to syntactic processing. The hypothesis is that the brain resources to plan and perform motor sequences are also involved in syntactic processing. To test this hypothesis, Event-Related brain Potentials (ERPs) were recorded while participants read sentences with embedded relative clauses, judging for their acceptability (half of the sentences contained a subject-verb morphosyntactic disagreement). The sentences, previously divided into three segments, were self-administered segment-by-segment in two different sequential manners: linear or non-linear. Linear self-administration consisted of successively pressing three buttons with three consecutive fingers in the right hand, while non-linear self-administration implied the substitution of the finger in the middle position by the right foot. Our aim was to test whether syntactic processing could be affected by the manner the sentences were self-administered. Main results revealed that the ERP's LAN component vanished whereas the P600 component increased in response to incorrect verbs, for non-linear relative to linear self-administration. The LAN and P600 components reflect early and late syntactic processing, respectively. Our results convey evidence that language syntactic processing and performing non-linguistic motor sequences may share resources in the human brain.



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On the role of V1 in avoiding obstacles

Publication date: Available online 15 November 2017
Source:Cortex
Author(s): Constanze Hesse, Jutta Billino, Thomas Schenk
This commentary is the next in a chain of events. First, Striemer, Chapman, and Goodale (2009) argued, on the basis of a single case study testing a patient with hemianopia, that the primary visual cortex (V1) is not essential for successful obstacle avoidance behaviour. In the Cortex special issue on the "what and how-pathways", we (Ross, Schenk, Billino, MacLeod, & Hesse, 2016) examined six patients suffering from hemianopia and came to the conclusion that obstacle avoidance during reaching crucially relies on input from V1. Subsequently, Striemer, Chapman, and Goodale (2017) have claimed that we misunderstood their original report. Clearly it is time that we get to the bottom of these misunderstandings and explore opportunities for finding common ground.In the introduction of our study (Ross et al., 2016) we presented several reasons for why Striemer et al.'s (2009) single-case study requires corroboration from similar findings in a group of patients with damage to their occipital cortex but intact subcortical visual pathways. Striemer et al (2017, section 2, 1^st paragraph). accept that our failure to replicate their original findings in a group of six patients (Ross et al., 2016) might constitute a serious challenge to the validity of their conclusions - but only if our study can be considered to be a fair test of their claims. In the rest of their commentary, Striemer et al. (2017) provide three main reasons for why our study does not provide such a fair test in their opinion. Firstly, they question the evidence from our patient study on the basis that our patients fail to fulfil the relevant conditions required for testing our hypothesis. Secondly, they suggest that we designed our experiments in ways that ensured a failure to replicate their original findings. Lastly, they argue that we misrepresented their position and attacked a straw man. In this commentary, we aim to demonstrate that (1) the disqualified evidence from our study can be recovered, (2) the methods used in our experiment have more redeeming aspects than granted; and finally, we assess the theoretical implications of Striemer et al.'s commentary for their original findings as well as for our study (3).



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Does observation of a disabled child’s action moderate action execution? Implication for the use of Action Observation Therapy for patient rehabilitation

Publication date: Available online 15 November 2017
Source:Cortex
Author(s): Marie Alsamour, Maxime Gilliaux, Anne Renders, Thierry Lejeune, Gaëtan Stoquart, Martin Gareth Edwards
BackgroundResearch investigating action observation-execution priming has mainly manipulated congruent versus incongruent action, and aspects of action expertise/capability. More specifically, the literature suggests enhanced performance priming following action observation by actors closely matched to participant expertise. The aim of the present study was to extend the understanding of action expertise effects by investigating action priming in healthy participants after observing a mild hemiparetic child actor versus a neurologically healthy child actor.Methods16 healthy right-handed children, aged 6 to 13 years were tested. Several motor assessments were performed, including gross and fine manual motor ability, and upper limb kinematics measured using a precise robotic device. A cross-over design consisted in two experimental conditions (observing actions performed by a child with hemiparesis versus observing actions performed by a healthy child) and a pre-observation double baseline control condition, with the data analyzed using repeated measures ANOVA.ResultsRelative to baseline, both types of action observation conditions enhanced fine manual dexterity, but observing the hemiparetic child enhanced gross manual dexterity and upper limb velocity kinematics relative to observing actions performed by a healthy child. No effects were shown on measures of smoothness and accuracy.DiscussionContradictorily to hypotheses discussed in the literature, results here showed evidence of enhanced action execution when healthy children observed hemiparetic compared to healthy child actions. These results are discussed in terms of how patient compared to healthy actors may be useful for clinical action observation priming therapy.



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AMPK: Sensing Glucose as well as Cellular Energy Status

Publication date: Available online 16 November 2017
Source:Cell Metabolism
Author(s): Sheng-Cai Lin, D. Grahame Hardie
Mammalian AMPK is known to be activated by falling cellular energy status, signaled by rising AMP/ATP and ADP/ATP ratios. We review recent information about how this occurs but also discuss new studies suggesting that AMPK is able to sense glucose availability independently of changes in adenine nucleotides. The glycolytic intermediate fructose-1,6-bisphosphate (FBP) is sensed by aldolase, which binds to the v-ATPase on the lysosomal surface. In the absence of FBP, interactions between aldolase and the v-ATPase are altered, allowing formation of an AXIN-based AMPK-activation complex containing the v-ATPase, Ragulator, AXIN, LKB1, and AMPK, causing increased Thr172 phosphorylation and AMPK activation. This nutrient-sensing mechanism activates AMPK but also primes it for further activation if cellular energy status subsequently falls. Glucose sensing at the lysosome, in which AMPK and other components of the activation complex act antagonistically with another key nutrient sensor, mTORC1, may have been one of the ancestral roles of AMPK.

Teaser

Recent findings show that AMPK, usually thought of as an energy sensor activated by changes in adenine nucleotides during metabolic stress, can also sense low availability of glucose via a novel, AMP-independent mechanism. Lin and Hardie review these latest developments and place them into context with the canonical energy-sensing mechanism.


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Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis

Publication date: Available online 16 November 2017
Source:Cell Metabolism
Author(s): Joan Sanchez-Gurmaches, Yuefeng Tang, Naja Zenius Jespersen, Martina Wallace, Camila Martinez Calejman, Sharvari Gujja, Huawei Li, Yvonne J.K. Edwards, Christian Wolfrum, Christian M. Metallo, Søren Nielsen, Camilla Scheele, David A. Guertin
Brown adipose tissue (BAT) is a therapeutic target for metabolic diseases; thus, understanding its metabolic circuitry is clinically important. Many studies of BAT compare rodents mildly cold to those severely cold. Here, we compared BAT remodeling between thermoneutral and mild-cold-adapted mice, conditions more relevant to humans. Although BAT is renowned for catabolic β-oxidative capacity, we find paradoxically that the anabolic de novo lipogenesis (DNL) genes encoding ACLY, ACSS2, ACC, and FASN were among the most upregulated by mild cold and that, in humans, DNL correlates with Ucp1 expression. The regulation and function of adipocyte DNL and its association with thermogenesis are not understood. We provide evidence suggesting that AKT2 drives DNL in adipocytes by stimulating ChREBPβ transcriptional activity and that cold induces the AKT2-ChREBP pathway in BAT to optimize fuel storage and thermogenesis. These data provide insight into adipocyte DNL regulation and function and illustrate the metabolic flexibility of thermogenesis.

Graphical abstract

Teaser

Sanchez-Gurmaches et al. reveal a mechanism by which AKT signaling and metabolism intersect through ChREBP in brown fat to simultaneously promote lipid synthesis and oxidation, a paradoxical and poorly understood feature of thermogenesis. This pathway is required for optimum brown fat function and conserved in humans.


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INSM1: A Novel Nuclear Marker in Merkel Cell Carcinoma (Cutaneous Neuroendocrine Carcinoma)

Merkel cell carcinoma (MCC) is a rare, clinically aggressive, cutaneous neuroendocrine (NE) neoplasm. As a tumor with small, round, blue cells, the histologic differential diagnosis for MCC can include melanoma, metastatic small cell carcinoma (SCC), nodular hematopoietic tumors, basal cell carcinoma (BCC), atypical variants of squamous carcinoma, and the uncommon occurrence of primary cutaneous Ewing sarcoma. In cases with atypical histology or without the classic immunophenotype the diagnosis can be challenging. Ultimately, immunohistochemistry (IHC) is essential to the definitive diagnosis of MCC, and in difficult cases the diagnosis may hinge entirely on the immunophenotype of the tumor cells. INSM1 is a transcription factor expressed in tissues undergoing terminal NE differentiation. As a nuclear protein tied both to differentiation and the cell-cycle, INSM1 may offer additional utility in comparison to traditional, cytoplasmic markers of NE differentiation.

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Scholar : These new articles for Environmental Claims Journal are available online

The online platform for Taylor & Francis Online content New for Environmental Claims Journal and online now on Taylor & Francis Online: Original Articles CERCLA Arranger Liability: Town of Islip v. Datre: What Intent is Required? Aaron Gershonowitz Pages: 1-9 | DOI: 10.1080/10406026.2017.1378565 Hoping to have your article read by anyone, anywhere and at any time? Find out more about publishing open access with Ecosystem Health and Sustainability. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Prognostic value of tumour-infiltrating lymphocytes in small HER2-positive breast cancer

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Carmen Criscitiello, Vincenzo Bagnardi, Giancarlo Pruneri, Andrea Vingiani, Angela Esposito, Nicole Rotmensz, Giuseppe Curigliano
BackgroundThe standard treatment for patients with small, node-negative, human epidermal growth factor receptor type 2 (HER2)–positive breast cancer (BC) is still controversial. Our aim was to assess the prognostic role of tumour-infiltrating lymphocytes (TILs) in patients with stage pT1a–b HER2-positive BC.Patients and methodsHaematoxylin and eosin slides from node-negative, pT1a–b HER2-positive BC surgical specimens were retrieved from pathology archives to assess TILs and their association with outcome.ResultsTILs were evaluated in 205 patients with HER2-positive, pT1a–b tumours, who underwent breast surgery between 1997 and 2009 at the European Institute of Oncology. At a median follow-up of 11 years, we did not observe any association between the presence of TILs, either assessed as a continuous or dichotomous variable (<50 versus ≥ 50%), and outcome. Within the subgroup of patients with pT1a tumours who did not receive any adjuvant therapy (36/97 patients), the rate of disease-free survival events was lower in lymphocyte-predominant BC (LPBC) as compared with non-LPBC patients (p = 0.066).ConclusionsTILs cannot be used as a prognostic biomarker in pT1a–b HER2-positive BC. Additional biomarkers are needed for selecting patients with stage I HER2-positive BC who candidate to adjuvant therapy de-escalation.



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Retrospective analysis of Austrian health recording data of antibiotic or nonantibiotic dry-off treatment on milk yield, somatic cell count, and frequency of mastitis in subsequent lactation

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): T. Wittek, A. Tichy, B. Grassauer, C. Egger-Danner
Typically, dairy cows are dried off at the end of lactation. During the dry period, intramammary infections may be cured or persist, and new infections may occur. Traditionally, antibiotics (AB) have been used at dry-off. However, blanket antibiotic dry-off treatment may no longer be justifiable and, recently, selective use of antibiotics at dry off has been proposed and different decision criteria suggested. The objective of the study was to evaluate cows receiving antibiotic treatment at dry off (AB group) compared with cows dried off without antibiotics (non-AB group) using a large data set. Primary outcome parameters were milk yield, somatic cell count (SCC), and frequency of mastitis in the subsequent lactation. Additionally, we aimed to calculate cut-off values to determine, at the cow level, whether antibiotic dry-off treatment is indicated. A data set of 88,534 lactations was used; 27,723 cows were dried off using antibiotics (AB group; 31.3%) and 60,811cows were dried off without antibiotics (non-AB group; 68.7%). Milk yield in previous and subsequent lactations was higher in the AB group. Cows in the AB group produced, on average, 91 kg more milk in the subsequent lactation. The average SCC during the final 90 d of the previous lactation and at dry-off did not differ between the 2 groups. The probability of drying off using antibiotics increased almost linearly with higher milk yield and with higher SCC. The use of antibiotics resulted in an average decrease in SCC of 1,500 cells/mL in the subsequent lactation. The frequency of clinical mastitis during the previous lactation was higher in the AB group than in the non-AB group. Independently of the dry-off treatment, this difference remained in the subsequent lactation within 90 d in milk. The use of antibiotics at dry-off had no significant effect on the frequency of mastitis within 90 d in milk of the subsequent lactation. The study indicates that Austrian farmers and veterinarians are applying selective dry-cow treatment using milk yield and, to a lesser extent, SCC and mastitis frequency, for decision-making. However, even though a large data set was used, cut-off values with sufficient diagnostic value for selective dry-cow treatment could not be identified. It is likely that cut-off values must be identified at the herd level or in combination with additional parameters (e.g., results of bacterial culture).



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Invited review: Practical feeding management recommendations to mitigate the risk of subacute ruminal acidosis in dairy cattle

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): E. Humer, R.M. Petri, J.R. Aschenbach, B.J. Bradford, G.B. Penner, M. Tafaj, K.-H. Südekum, Q. Zebeli
Rumen health is of vital importance in ensuring healthy and efficient dairy cattle production. Current feeding programs for cattle recommend concentrate-rich diets to meet the high nutritional needs of cows during lactation and enhance cost-efficiency. These diets, however, can impair rumen health. The term "subacute ruminal acidosis" (SARA) is often used as a synonym for poor rumen health. In this review, we first describe the physiological demands of cattle for dietary physically effective fiber. We also provide background information on the importance of enhancing salivary secretions and short-chain fatty acid absorption across the stratified squamous epithelium of the rumen; thus, preventing the disruption of the ruminal acid–base balance, a process that paves the way for acidification of the rumen. On-farm evaluation of dietary fiber adequacy is challenging for both nutritionists and veterinarians; therefore, this review provides practical recommendations on how to evaluate the physical effectiveness of the diet based on differences in particle size distribution, fiber content, and the type of concentrate fed, both when the latter is part of total mixed ration and when it is supplemented in partial mixed rations. Besides considering the absolute amount of physically effective fiber and starch types in the diet, we highlight the role of several feeding management factors that affect rumen health and should be considered to control and mitigate SARA. Most importantly, transitional feeding to ensure gradual adaptation of the ruminal epithelium and microbiota; monitoring and careful management of particle size distribution; controlling feed sorting, meal size, and meal frequency; and paying special attention to primiparous cows are some of the feeding management tools that can help in sustaining rumen health in high-producing dairy herds. Supplementation of feed additives including yeast products, phytogenic compounds, and buffers may help attenuate SARA, especially during stress periods when the risk of a deficiency of physically effective fiber in the diet is high, such as during early lactation. However, the usage of feed additives cannot fully compensate for suboptimal feeding management.



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Minimum inhibitory concentrations of frequently used antibiotics against Escherichia coli and Trueperella pyogenes isolated from uteri of postpartum dairy cows

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): A. Pohl, A. Lübke-Becker, W. Heuwieser
The objective of this study was to determine minimum inhibitory concentrations (MIC) of frequently used antimicrobials for Escherichia coli and Trueperella pyogenes isolated from postpartum bovine uteri of cows with acute puerperal metritis (APM, n = 67), cows suspected to have APM (n = 37), and healthy cows (n = 37) and to evaluate possible differences in MIC according to clinical signs. Cows with APM had reddish-brown, fetid vaginal discharge and rectal temperature (RT) ≥39.5°C within 21 d in milk; cows suspected to have APM had either reddish-brown, fetid vaginal discharge or RT ≥39.5°C within 21 d in milk; and healthy cows had neither fetid discharge nor RT ≥39.5°C. Samples were collected from cows on commercial dairy herds (n = 7) using the cytobrush technique. A total of 37 T. pyogenes isolates and 85 E. coli isolates were tested. Ceftiofur, a third-generation cephalosporin that is often used to treat APM, was the focus of analysis. Trueperella pyogenes and E. coli were isolated more often from samples of cows with APM (46 and 90%, respectively) compared with samples from healthy cows (19 and 54%, respectively). Regarding cows suspected to have APM, T. pyogenes and E. coli were numerically more often isolated (30 and 70%, respectively) than in healthy cows (19 and 54%, respectively). Minimum inhibitory concentrations of ceftiofur were low. For T. pyogenes and E. coli, MIC50 (concentration that inhibited growth of 50% of isolates) were 0.25 and 0.5 µg/mL and MIC90 (concentration that inhibited growth of 90% of isolates) were 0.5 and 1 µg/mL, respectively. Although ceftiofur inhibited all T. pyogenes at the highest concentration tested (64 µg/mL), the growth of 5.9% of E. coli was not impaired. Recently, ampicillin has been suggested as an alternative treatment for APM. Although the T. pyogenes isolates exhibited low MIC in general (MIC50 ≤0.015 µg/mL and MIC90 = 0.06 µg/mL) and 81.1% of all T. pyogenes could be inhibited at the lowest ampicillin concentration tested, 11.8% of the E. coli isolates were not impaired at the highest concentration (64 µg/mL) tested in this study. The MIC50 and MIC90 of E. coli were 4 and ≥128 µg/mL, respectively. We detected no difference in the MIC distributions of ceftiofur or ampicillin among isolates from the 3 APM groups. In summary, E. coli with high MIC against ceftiofur as well as against ampicillin were found in this study.



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Biofilm formation of Staphylococcus aureus dairy isolates representing different genotypes

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): E. Thiran, P.A. Di Ciccio, H.U. Graber, E. Zanardi, A. Ianieri, J. Hummerjohann
The objective of this study was to compare the biofilm-forming capabilities of different genotypes of Staphylococcus aureus dairy isolates from Switzerland and northern Italy, including Staph. aureus genotype B (GTB) and methicillin-resistant Staph. aureus (MRSA). We hypothesized that biofilm formation might be more pronounced in the contagious GTB isolates compared with other genotypes affecting individual animals. Twenty-four dairy isolates, including 9 MRSA, were further characterized by genotyping by using ribosomal spacer PCR, spa typing, biofilm formation under static and dynamic conditions, and scanning electron microscopy. The GTB isolates (n = 6) were more able to form biofilms than other genotypes at 37°C and at 20°C after 48 and 72 h of incubation in the static assay using polystyrene microtiter plates. This result was supported by scanning electron micrographs showing a GTB isolate producing strong biofilm with extracellular matrix in contrast to a genotype C isolate. Furthermore, none of the MRSA isolates formed strong biofilms in the static assay. However, some MRSA produced low or moderate amounts of biofilm depending on the applied conditions. Under dynamic conditions, a much more diverse situation was observed. The ability of GTB isolates to be strong biofilm formers was not observed in all cases, emphasizing the importance of growth conditions for the expression of biofilm-related genes. No specific genotype, spa type, or MRSA isolate could be categorized significantly into one level of biofilm formation. Nineteen percent of isolates behaved similarly under static and dynamic conditions. The results of this study expand our knowledge of different dairy-related Staph. aureus subtypes and indicate the benefit of genotyping when biofilms are studied.



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Uncertainty assessment of the breath methane concentration method to determine methane production of dairy cows

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): Liansun Wu, Peter W.G. Groot Koerkamp, Nico Ogink
The breath methane concentration method uses the methane concentrations in the cow's breath during feed bin visits as a proxy for the methane production rate. The objective of this study was to assess the uncertainty of a breath methane concentration method in a feeder and its capability to measure and rank cows' methane production. A range of controlled methane fluxes from a so-called artificial reference cow were dosed in a feed bin, and its exhaled air was sampled by a tube inside the feeder and analyzed. The artificial reference cow simulates the lungs, respiratory tract, and rumen of a cow and releases a variable methane flux to generate a concentration pattern in the exhaled breath that closely resembles a real cow's pattern. The strength of the relation between the controlled methane release rates of the artificial reference cow and the measured methane concentrations was analyzed by linear regression, using the coefficient of determination (R²) and the residual standard error as performance indicators. The effect of error sources (source-sampling distance, air turbulence, and cow's head movement) on this relation was experimentally investigated, both under laboratory and barn conditions. From the laboratory to the dairy barn at the 30-cm sampling distance, the R²-value decreased from 0.97 to 0.37 and the residual standard error increased from 75 to 86 ppm as a result of barn air turbulence, the latter increasing to a theoretical 94 ppm if modeled variability due to cow's head movement was accounted for as well. In practice, the effect of these random errors can be compensated by sampling strategies including repeated measurements on each cow over time, thus increasing the distinctive power between cows. However, systematic errors that may disturb the relation between concentration and production rate, such as cow variation in air exhalation rate and air flow patterns around sampling locations that differ between barns, cannot be compensated by repeated measurements. As a result, the methane concentrations of breath air will vary between cows with the same methane production. We conclude that the capability of the breath concentration measurement method to adequately measure and rank methane production rates among cows is highly uncertain and requires further investigation into variation sources with a systematic nature.



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Determination of fat, protein, moisture, and salt content of Cheddar cheese using mid-infrared transmittance spectroscopy

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): Brenda J. Margolies, David M. Barbano
The objective of our work was to develop and evaluate the performance of a rapid method for measuring fat, protein, moisture, and salt content of Cheddar cheese using a combination mid-infrared (MIR) transmittance analysis and an in-line conductivity sensor in an MIR milk analyzer. Cheddar cheese was blended with a dissolving solution containing pentasodium triphosphate and disodium metasilicate to achieve a uniform, particle-free dispersion of cheese, which had a fat and protein content similar to milk and could be analyzed using a MIR transmittance milk analyzer. Annatto-colored Cheddar cheese samples (34) from one cheese factory were analyzed using reference chemistry methods for fat (Mojonnier ether extraction), crude protein (Kjeldahl), moisture (oven-drying total solids), and salt (Volhard silver nitrate titration). The same 34 cheese samples were also dissolved using the cheese dissolver solution, and then run through the MIR and used for calibration. The reference testing for fat and crude protein was done on the cheese after dispersion in the dissolver solution. Validation was done using a total of 36 annatto-colored Cheddar cheese samples from 4 cheese factories. The 36 validation cheese samples were also analyzed using near-infrared spectroscopy for fat, moisture, and the coulometric method for salt in each factory where they were produced. The validation cheeses were also tested using the same chemical reference methods that were used for analysis of the calibration samples. Standard error of prediction (SEP) values for moisture and fat on the near-infrared spectroscopy were 0.30 and 0.45, respectively, whereas the MIR produced SEP values of 0.28 and 0.23 for moisture (mean 36.82%) and fat (mean 34.0%), respectively. The MIR also out-performed the coulometric method for salt determination with SEP values of 0.036 and 0.139 at a mean level of salt of 1.8%, respectively. The MIR had an SEP value of 0.19 for estimation at a mean level of 24.0% crude protein, which suggests that MIR could be an easy and effective way for cheese producers to measure protein to determine protein recovery in cheese making.



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Physicochemical and sensory properties of yogurts containing sacha inchi (Plukenetia volubilis L.) seeds and β-glucans from Ganoderma lucidum

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): Ana-Milena Vanegas-Azuero, Luis-Felipe Gutiérrez
Dairy products have been widely used for adding various biomolecules with the aim of improving their functional properties and health benefits. In this study, the physicochemical properties and sensory acceptance of yogurts enriched with sacha inchi (Plukenetia volubilis) seeds (SIS) and β-glucans from Ganoderma lucidum (BGGL) were investigated. The angiotensin-converting enzyme–inhibitory activity of some yogurt samples was also evaluated. Yogurts were produced from reconstituted skim milk powder, and SIS (4% wt/wt) and BGGL were added at different concentrations (0–1.5% wt/wt). The fermentation kinetics were not affected by the enrichment process. The addition of SIS and BGGL significantly increased (P < 0.05) the contents of protein, fat, carbohydrates, ash, total solids, aspartic acid, serine, arginine, glycine, threonine, tyrosine, and alanine. α-Linolenic (49.3%) and linoleic (32.2%) acids were the main fatty acids found in the enriched samples, whose values were about 50- and 25-fold higher than those of the control yogurt. The textural parameters (firmness, consistency, cohesiveness, and index of viscosity) of the enriched yogurts were significantly lower (P < 0.05) than those of the control samples during the whole storage period. All enriched yogurts showed a sensorial acceptance higher than 70% by untrained panelists. The angiotensin-converting enzyme–inhibitory activity of some selected yogurt samples ranged between 36 and 59%. These results indicate that SIS and BGGL could be used as natural ingredients for improving the nutritional value of yogurt and fermented milks.



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Short communication: Growth of dairy isolates of Geobacillus thermoglucosidans in skim milk depends on lactose degradation products supplied by Anoxybacillus flavithermus as secondary species

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): Y. Zhao, M. Kumar, M.P.M. Caspers, M.N. Nierop Groot, J.M.B.M. van der Vossen, T. Abee
Thermophilic bacilli such as Anoxybacillus and Geobacillus are important contaminants in dairy powder products. Remarkably, one of the common contaminants, Geobacillus thermoglucosidans, showed poor growth in skim milk, whereas significant growth of G. thermoglucosidans was observed in the presence of an Anoxybacillus flavithermus dairy isolate. In the present study, we investigated the underlying reason for this growth dependence of G. thermoglucosidans. Whole-genome sequences of 4 A. flavithermus strains and 4 G. thermoglucosidans strains were acquired, with special attention given to carbohydrate utilization clusters and proteolytic enzymes. Focusing on traits relevant for dairy environments, comparative genomic analysis revealed that all G. thermoglucosidans strains lacked the genes necessary for lactose transport and metabolism, showed poor growth in skim milk, and produced white colonies on X-gal plates, indicating the lack of β-galactosidase activity. The A. flavithermus isolates scored positive in these tests, consistent with the presence of a putative lactose utilization gene cluster. All tested isolates from both species showed proteolytic activity on milk plate count agar plates. Adding glucose or galactose to liquid skim milk supported growth of G. thermoglucosidans isolates, in line with the presence of the respective monosaccharide utilization gene clusters in the genomes. Analysis by HPLC of A. flavithermus TNO-09.006 culture filtrate indicated that the previously described growth dependence of G. thermoglucosidans in skim milk was based on the supply of glucose and galactose by A. flavithermus TNO-09.006.



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Rapid species- and subspecies-specific level classification and identification of Lactobacillus casei group members using MALDI Biotyper combined with ClinProTools

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): Chien-Hsun Huang, Lina Huang
Using common taxonomic methods such as 16S rDNA sequencing and physiological and biochemical analysis to identify members of the Lactobacillus casei group (LCG) is time-consuming, expensive and inaccurate. In this study, we applied matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to rapid discriminate LCG strains by creating an analytical in-house database (IHDB) and to develop a classification model for subspecies-level differentiation based on MS biomarkers using ClinProTools bioinformatics software (Bruker Daltonics, Billerica, MA). Genotypic methods (housekeeping gene sequencing and species-specific PCR) were also established to validate the MALDI-TOF MS platform. A total of 48 LCG reference strains were correctly identified at the species level (mean score: 2.45 ± 0.1) by using MALDI-TOF MS with an IHDB and had high score values, which was in accordance with results from mutL gene sequencing and specific PCR-based methods. However, one strain that was identified as L. casei had a relatively low score value (2.02 ± 0.02), lower sequence similarities (mutL: 90.4%), and failed to amplify a species-specific amplicon; it may therefore represent an undescribed novel species. In addition, after implementation of the classification model (based on 2 biomarker peaks: m/z 4,930 and 5,303), L. paracasei strains could be clearly and easily differentiated to the subspecies level. Afterward, 7 LCG-related isolates from different probiotic samples were analyzed and accurately identified. Our data demonstrate the high-resolution performance of MALDI-TOF MS for fast and accurate demarcation of LCG strains when used with an IHDB coupled to ClinProTools; this methodology can serve as an alternative for quality control of probiotic products.



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Modeling greenhouse gas emissions from dairy farms

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): C. Alan Rotz
Dairy farms have been identified as an important source of greenhouse gas emissions. Within the farm, important emissions include enteric CH4 from the animals, CH4 and N2O from manure in housing facilities during long-term storage and during field application, and N2O from nitrification and denitrification processes in the soil used to produce feed crops and pasture. Models using a wide range in level of detail have been developed to represent or predict these emissions. They include constant emission factors, variable process-related emission factors, empirical or statistical models, mechanistic process simulations, and life cycle assessment. To fully represent farm emissions, models representing the various emission sources must be integrated to capture the combined effects and interactions of all important components. Farm models have been developed using relationships across the full scale of detail, from constant emission factors to detailed mechanistic simulations. Simpler models, based upon emission factors and empirical relationships, tend to provide better tools for decision support, whereas more complex farm simulations provide better tools for research and education. To look beyond the farm boundaries, life cycle assessment provides an environmental accounting tool for quantifying and evaluating emissions over the full cycle, from producing the resources used on the farm through processing, distribution, consumption, and waste handling of the milk and dairy products produced. Models are useful for improving our understanding of farm processes and their interacting effects on greenhouse gas emissions. Through better understanding, they assist in the development and evaluation of mitigation strategies for reducing emissions and improving overall sustainability of dairy farms.



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Determination of lactadherin concentration in dairy by-products by ELISA: Effect of heat treatment and hydrolysis

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): Daniel Ripollés, José A. Parrón, Javier Fraguas, Miguel Calvo, María D. Pérez, Lourdes Sánchez
Lactadherin is a peripheral glycoprotein of the milk fat globule membrane with several attributed biological activities. In this study, we developed an indirect competitive ELISA to determine lactadherin concentration by using a rabbit polyclonal antiserum. The ELISA was applied to quantify lactadherin in several dairy by-products. Of the products tested, raw and commercial buttermilk had the highest concentrations of lactadherin (6.79 and 5.27 mg/g of product, respectively), followed by commercial butter serum (4.86 mg/g), commercial skim milk (4.84 mg/g), and raw whey (1.20 mg/g). The concentration of immunoreactive lactadherin was also determined in dairy by-products after they were subjected to different technological treatments. Thus, raw products were heat treated at combinations of temperature and time typically used in the dairy industry, and commercial products were hydrolyzed using 3 proteolytic enzyme preparations. Heat treatments of whey and buttermilk resulted in a smaller decrease in lactadherin concentration than did hydrolysis as determined by ELISA and electrophoresis. At high temperatures for long durations, the loss of lactadherin was higher in whey than in buttermilk, with the maximal reduction of around 48% found after treating whey at 72°C for 60 min. Hydrolysis of commercial products with proteolytic enzymes resulted in a marked decrease of immunoreactivity within the first 5 min of treatment, which thereafter was constant throughout 4 h of hydrolysis. These results demonstrate that dairy by-products from milk fat processing are good natural sources of lactadherin, although technological processes have to be considered, because they have different effects on lactadherin content.



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Short communication: Detection of lameness in dairy cows using a grooming device

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): R. Mandel, H. Harazy, L. Gygax, C.J. Nicol, A. Ben-David, H.R. Whay, E. Klement
Lameness in dairy cattle is a common welfare problem with significant economic implications. All too often, appropriate treatment is delayed or neglected due to insufficient detection of lame cows. Brush usage is considered a low-resilience activity; that is, one that typically decreases when energy resources are limited or when the cost involved in the activity increases, such as during sickness and stress. The aim of this study was to determine the association between brush usage and different degrees of lameness. Locomotion scores of 209 lactating Holstein dairy cows were collected individually once a week for 14 consecutive weeks, using a 5-point visual assessment scoring system (1 = nonlame, 2 = uneven gait, 3 = mild lameness, 4 = lameness, 5 = severe lameness). Daily brush usage was collected automatically from 3 cowsheds of similar size and structure located on a commercial dairy farm. In each of the 3 cowsheds, 2 brushes were installed, one next to the feed bunk, and the other away from the feed bunk (on the opposite side of the cowshed). Linear and generalized linear mixed-effects models were used to evaluate the association between locomotion scores and daily measures of brush usage. We found a significant interaction between locomotion score and brush location (near to/distant from feed bunk) on the daily proportion of cows using the brush at least once and on daily duration of brush usage. Specifically, we showed that lame and severely lame cows did not use brushes that were installed away from the feed bunk but continued to use brushes that were installed next to the feed bunk. Brush usage by cows with uneven gait (locomotion score 2) or with mild lameness (locomotion score 3) did not differ from that of nonlame cows (locomotion score 1). The results of this study suggest that monitoring of daily usage of brushes located away from the feed bunk could be a useful method for detecting lameness and severe lameness in dairy cows. However, the use of this method to detect mild lameness or cases of abnormal gait is, at this stage, less promising.



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Evaluation of carinata meal as a feedstuff for growing dairy heifers: Effects on growth performance, rumen fermentation, and total-tract digestibility of nutrients

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): K. Rodriguez-Hernandez, J.L. Anderson
Our objective was to determine the effects of feeding carinata meal (CRM) compared with distillers dried grains with solubles (DDGS) on growth performance, rumen fermentation, and nutrient utilization in peripubertal dairy heifers. A 16-wk randomized block design experiment with 24 Holstein heifers [6.6 ± 0.7 mo and 218 ± 27 kg of body weight (BW)] was conducted. Treatments diets were (1) 10% cold-pressed CRM and (2) 10% DDGS on a dry matter (DM) basis. The remainder of the diets consisted of grass hay, ground corn, soybean meal, and mineral mix. Diets were formulated to be isonitrogenous and isocaloric. Heifers were individually fed using a Calan gate feeding system, and the rations were limit-fed at 2.65% of BW on a DM basis to target a 0.8 kg/d of average daily gain. Heifers were weighed every 2 wk and the ration amount offered was adjusted accordingly. Frame sizes, BW, and body condition scores were measured 2 d every 2 wk throughout the study. During wk 12 and 16, rumen fluid samples were collected via esophageal tubing for pH, ammonia N, and volatile fatty acid analyses. In wk 16, fecal grab samples were collected for apparent total-tract digestibility estimation. Heifer DM intake, BW, average daily gain, and gain:feed were similar between treatments. No differences were observed between treatments in frame measurements or body condition scores. Rumen pH tended to be greater in CRM compared with DDGS. Rumen ammonia N and total volatile fatty acid concentration were not different between treatments. Apparent total-tract digestibility of DM, neutral detergent fiber, and acid detergent fiber were decreased in CRM compared with DDGS. A tendency was detected for reduced organic matter digestibility in CRM. No difference was observed between treatments for crude protein total-tract digestibility. However, these differences in total-tract nutrient digestibility were not large enough to influence growth performance. Overall, results demonstrated that growing heifers can be limit-fed diets with 10% CRM and maintain growth performance compared with a control diet containing 10% DDGS.



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Dose- and type-dependent effects of long-chain fatty acids on adipogenesis and lipogenesis of bovine adipocytes

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): Chen Yanting, Q.Y. Yang, G.L. Ma, M. Du, J.H. Harrison, E. Block
Differentiation and lipid metabolism of adipocytes have a great influence on milk performance, health, and feed efficiency of dairy cows. The effects of dietary long-chain fatty acids (FA) on adipogenesis and lipogenesis of dairy cows are often confounded by other nutritional and physiological factors in vivo. Therefore, this study used an in vitro approach to study the effect of dose and type of long-chain FA on adipogenesis and lipogenesis of bovine adipocytes. Stromal vascular cells were isolated from adipose tissue of dairy cows and induced into mature adipocytes in the presence of various long-chain FA including myristic, palmitic, stearic, oleic, or linoleic acid. When concentrations of myristic, palmitic, and oleic acids in adipogenic mediums were 150 and 200 μM, the induced mature adipocytes had greater lipid content compared with other concentrations of FA. In addition, mature adipocytes induced at 100 μM stearic acid and 300 μM linoleic acid had the greatest content of lipid than at other concentrations. High concentrations of saturated FA were more toxic for cells than the same concentration of unsaturated FA during the induction. When commitment stage was solely treated with FA, the number of differentiated mature adipocytes was greater for oleic and linoleic acids than other FA. When the maturation stage was treated with FA, the number of mature adipocytes was not affected, but the lipid content in adipocytes was affected and ranked oleic > linoleic > myristic > stearic > palmitic. In summary, this study showed that adipogenesis and lipogenesis of bovine adipocytes were differentially affected by long-chain FA, with unsaturated FA more effective than saturated FA.



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Economic and genetic performance of various combinations of in vitro-produced embryo transfers and artificial insemination in a dairy herd

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): Karun Kaniyamattam, Jeremy Block, Peter J. Hansen, Albert De Vries
The objective of this study was to find the optimal proportions of pregnancies from an in vitro-produced embryo transfer (IVP-ET) system and artificial insemination (AI) so that profitability is maximized over a range of prices for embryos and surplus dairy heifer calves. An existing stochastic, dynamic dairy model with genetic merits of 12 traits was adapted for scenarios where 0 to 100% of the eligible females in the herd were impregnated, in increments of 10%, using IVP-ET (ET0 to ET100, 11 scenarios). Oocytes were collected from the top donors selected for the trait lifetime net merit (NM$) and fertilized with sexed semen to produce IVP embryos. Due to their greater conception rates, first ranked were eligible heifer recipients based on lowest number of unsuccessful inseminations or embryo transfers, and then on age. Next, eligible cow recipients were ranked based on the greatest average estimated breeding values (EBV) of the traits cow conception rate and daughter pregnancy rate. Animals that were not recipients of IVP embryos received conventional semen through AI, except that the top 50% of heifers ranked for EBV of NM$ were inseminated with sexed semen for the first 2 AI. The economically optimal proportions of IVP-ET were determined using sensitivity analysis performed for 24 price sets involving 6 different selling prices of surplus dairy heifer calves at approximately 105 d of age and 4 different prices of IVP embryos. The model was run for 15 yr after the start of the IVP-ET program for each scenario. The mean ± standard error of true breeding values of NM$ of all cows in the herd in yr 15 was greater by $603 ± 2 per cow per year for ET100 when compared with ET0. The optimal proportion of IVP-ET ranged from ET100 (for surplus dairy heifer calves sold for ≥$300 along with an additional premium based on their EBV of NM$ and a ≤$100 embryo price) to as low as ET0 (surplus dairy heifer calves sold at $300 with a $200 embryo price). For the default assumptions, the profit/cow in yr 15 was greater by $337, $215, $116, and $69 compared with ET0 when embryo prices were $50, $100, $150, and $200. The optimal use of IVP-ET was 100, 100, 62, and 36% of all breedings for these embryo prices, respectively. At the input price of $165 for an IVP embryo, the difference in the net present value of yr 15 profit between ET40 (optimal scenario) and ET0 was $33 per cow. In conclusion, some use of IVP-ET was profitable for a wide range of IVP-ET prices and values of surplus dairy heifer calves.



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Daily and seasonal trends of electricity and water use on pasture-based automatic milking dairy farms

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): J. Shortall, B. O'Brien, R.D. Sleator, J. Upton
The objective of this study was to identify the major electricity and water-consuming components of a pasture-based automatic milking (AM) system and to establish the daily and seasonal consumption trends. Electricity and water meters were installed on 7 seasonal calving pasture-based AM farms across Ireland. Electricity-consuming processes and equipment that were metered for consumption included milk cooling components, air compressors, AM unit(s), auxiliary water heaters, water pumps, lights, sockets, automatic manure scrapers, and so on. On-farm direct water-consuming processes and equipment were metered and included AM unit(s), auxiliary water heaters, tubular coolers, wash-down water pumps, livestock drinking water supply, and miscellaneous water taps. Data were collected and analyzed for the 12-mo period of 2015. The average AM farm examined had 114 cows, milking with 1.85 robots, performing a total of 105 milkings/AM unit per day. Total electricity consumption and costs were 62.6 Wh/L of milk produced and 0.91 cents/L, respectively. Milking (vacuum and milk pumping, within-AM unit water heating) had the largest electrical consumption at 33%, followed by air compressing (26%), milk cooling (18%), auxiliary water heating (8%), water pumping (4%), and other electricity-consuming processes (11%). Electricity costs followed a similar trend to that of consumption, with the milking process and water pumping accounting for the highest and lowest cost, respectively. The pattern of daily electricity consumption was similar across the lactation periods, with peak consumption occurring at 0100, 0800, and between 1300 and 1600 h. The trends in seasonal electricity consumption followed the seasonal milk production curve. Total water consumption was 3.7 L of water/L of milk produced. Water consumption associated with the dairy herd at the milking shed represented 42% of total water consumed on the farm. Daily water consumption trends indicated consumption to be lowest in the early morning period (0300–0600 h), followed by spikes in consumption between 1100 and 1400 h. Seasonal water trends followed the seasonal milk production curve, except for the month of May, when water consumption was reduced due to above-average rainfall. This study provides a useful insight into the consumption of electricity and water on a pasture-based AM farms, while also facilitating the development of future strategies and technologies likely to increase the sustainability of AM systems.



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Subacute ruminal acidosis affects fermentation and endotoxin concentration in the rumen and relative expression of the CD14/TLR4/MD2 genes involved in lipopolysaccharide systemic immune response in dairy cows

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): B. Stefanska, W. Człapa, E. Pruszynska-Oszmałek, D. Szczepankiewicz, V. Fievez, J. Komisarek, K. Stajek, W. Nowak
The first objective of this study was to investigate the effects of subacute ruminal acidosis (SARA) on fermentation, ruminal free lipopolysaccharides (LPS), and expression of the cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR4), and myeloid differentiation protein 2 (MD2) complex in white blood cells involved in the systemic immune response in dairy cows. The second objective was a study of whether increased expression of the LPS receptor complex led to increases in the concentrations of plasma high-density lipoprotein (HDL) and serum Ca. Three hundred five dairy cows located in 13 Polish high-yielding dairy commercial farms were selected according to their days in milk (40–150 d; average = 75), 305-d milk yield (10,070–12,041 kg; average = 10,940), and number of lactations (primiparous, n = 139 and multiparous, n = 166). Next, the herds were segregated into 3 groups based on the percentages of cows with an assigned value of ruminal fluid pH: SARA-positive, SARA-risk, and SARA-negative herds. Moreover, 305 selected dairy cows were divided according to the classification based on ruminal fluid pH into 3 groups as healthy (pH >5.81), risk (pH 5.8–5.6) and acidotic cows (pH <5.6). Rumen fluid samples were collected via rumenocentesis. In the AC group, we recorded higher concentrations of ruminal free LPS [4.57 Log10 endotoxin units (EU)/mL; 42,206 EU/mL] compared with the healthy group (4.48 Log10 EU/mL; 34,179 EU/mL). Similarly, the concentration of ruminal free LPS was higher in SARA-positive herds (4.60 Log10 EU/mL; 43,000 EU/mL) compared with SARA-negative herds (4.47 Log10 EU/mL; 32,225 EU/mL). The relative mRNA abundance of genes associated with the function of LPS receptors, such as CD14, TLR4, and MD2, in white blood cells differed between all experimental groups on both cow and herd levels. In the acidotic group, we recorded higher concentrations of HDL (78.16 vs. 68.32 mg/dL) and serum amyloid A (10.80 vs. 9.16 µg/mL) and lower concentrations of Ca (8.26 vs. 10.16 mg/dL) and haptoglobin (470.19 vs. 516.85 ng/mL) compared with the healthy group. Similar results were obtained in the SARA herd status analysis, but the concentration of lipopolysaccharide-binding protein differed statistically. Moreover, the pH of ruminal fluid was negatively correlated with relative mRNA abundance of genes such as CD14, TLR4, MD2, and concentrations of serum HDL and serum amyloid A, although positively correlated with serum Ca. The results indicated that decreases in ruminal fluid pH increased the release of free LPS into the rumen and stimulated the expression of the LPS receptor complex and immune response. Moreover, an increase in the expression of the LPS receptor led to higher concentrations of plasma HDL and lower serum Ca, which may be a protective mechanism against endotoxemia. However, the biological significance of these results needs to be investigated further in larger field trials.



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Efficacy of colostrum replacer versus maternal colostrum on immunological status, health, and growth of preweaned dairy calves

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): A. Lago, M. Socha, A. Geiger, D. Cook, N. Silva-del-Río, C. Blanc, R. Quesnell, C. Leonardi
Commercially available colostrum replacers (CR) are commonly used when maternal colostrum (MC) is unavailable, for managerial convenience, to ensure quality consistency at first feeding, or in disease control and eradication programs. The objective of this study was to determine the efficacy of feeding First Day Formula (Accelerated Genetics, Baraboo, WI) CR versus pooled MC on immunological status, growth, and health of preweaned dairy calves. A total of 1,220 Jersey and Jersey × Holstein calves born on a California Central Valley dairy farm were assigned after birth to receive either CR or MC following a systematic allocation procedure. Calves assigned to MC were tube fed 2.8 L of MC, and calves assigned to CR were tube fed a total of 500 g of CR (150 g of immunoglobulin G; IgG) mixed into 1.9 L of water at 1 h ± 5 min after the calf was born. A subset of calves was selected for passive transfer (n = 592) and growth (n = 268) analyses. Although both coliform count and total bacteria count were low for MC and CR fed to calves during the study, the predicted probability of calves receiving contaminated liquid feed (coliform count >10,000 cfu/mL) at first feeding was reduced for calves fed CR (1.5%) compared with calves fed MC (6.1%). The mean blood concentration of IgG was lower for calves fed CR than for calves fed MC (19.6 vs. 23.4 mg/mL). However, the apparent efficiency of absorption of IgG did not differ between treatments (34.4 and 35.9% for CR and MC, respectively). Total proteins were lower in calves fed CR compared with MC at 24 h (5.16 vs. 5.84 g/dL, respectively). Calves fed CR were 1.5 kg lighter at weaning and gained 0.03 kg less per day (0.30 vs. 0.33 kg/d, respectively) than calves fed MC before weaning. Height at weaning did not differ between the 2 treatment groups. Calves fed CR tended to have a higher predicted probability of not being treated for diarrhea than calves fed MC (0.142 vs. 0.110, respectively). However, when the disease was present, CR had a higher number of treatment days compared with MC (11.6 vs. 10.8 d, respectively). The hazard ratio of dying did not differ between MC and CR; however, CR calves had a numerically higher risk (hazard ratio = 1.347) of dying compared with calves that received MC. In conclusion, IgG absorption and serum concentration of calves were adequate when calves were fed either CR or MC. The CR-fed calves had a lower probability of receiving contaminated liquid feed and performed similar in terms of health compared with calves receiving high-quality MC, although they were slightly lighter at weaning. Therefore, the CR evaluated in this study is a valid alternative to high-quality (>50 mg of IgG/mL) MC.



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Association of milking interval and milk production rate in an automatic milking system

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): J.F. Penry, P.M. Crump, L.L. Hernandez, D.J. Reinemann
The primary aim of this research was to describe the association between milking interval (MI) and milk production rate (MPR) at the quarter level in a large commercial farm using an automatic milking system. A secondary aim was to determine whether a 2-h decrease in MI would increase MPR at the cow level in midlactation multiparous cows. Six months of data from 1,280 cows were used to assess the association between MI (h) and quarter MPR (kg/h). Increasing MI was associated with decreased MPR for early, mid, and late lactation, both primiparous and multiparous cows, and all 4 quarter positions and across time. The decrease in MPR is approximately 2%/h of increasing MI for multiparous cows and 1.5%/h for primiparous cows. Regardless of quarter, multiparous cows had a greater MPR than primiparous cows, and rear quarters had greater MPR than front quarters. An experiment to test the causal relationship between changing MI and cow-level MPR was conducted using 26 animal pairs matched on MI, days in milk, and milk yield. During the 21-d treatment period, the average MI of treatment cows was decreased by 2.4 h compared with control cows. In both the 21-d treatment and 42-d posttreatment periods, no significant difference was found in cow-level MPR between the treatment and control groups. Despite the negative association between increasing MI and MPR being consistent across all assessed days in milk windows and all quarters, results from this experiment suggest that intervention to decrease MI might require an MI change greater than 2 h or be applied in early lactation to significantly increase MPR.



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Short communication: Genomic prediction using imputed whole-genome sequence variants in Brown Swiss Cattle

Publication date: Available online 15 November 2017
Source:Journal of Dairy Science
Author(s): Mirjam Frischknecht, Theodorus H.E. Meuwissen, Beat Bapst, Franz R. Seefried, Christine Flury, Dorian Garrick, Heidi Signer-Hasler, Christian Stricker, Anna Bieber, Ruedi Fries, Ingolf Russ, Johann Sölkner, Alessandro Bagnato, Birgit Gredler-Grandl
The accuracy of genomic prediction determines response to selection. It has been hypothesized that accuracy of genomic breeding values can be increased by a higher density of variants. We used imputed whole-genome sequence data and various single nucleotide polymorphism (SNP) selection criteria to estimate genomic breeding values in Brown Swiss cattle. The extreme scenarios were 50K SNP chip data and whole-genome sequence data with intermediate scenarios using linkage disequilibrium-pruned whole-genome sequence variants, only variants predicted to be missense, or the top 50K variants from genome-wide association studies. We estimated genomic breeding values for 3 traits (somatic cell score, nonreturn rate in heifers, and stature) and found differences in accuracy levels between traits. However, among different SNP sets, accuracy was very similar. In our analyses, sequence data led to a marginal increase in accuracy for 1 trait and was lower than 50K for the other traits. We concluded that the inclusion of imputed whole-genome sequence data does not lead to increased accuracy of genomic prediction with the methods.



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A novel, modernized Golgi-Cox stain optimized for CLARITY cleared tissue

Publication date: Available online 15 November 2017
Source:Journal of Neuroscience Methods
Author(s): Mustafa S. Kassem, Sandra Y.Y. Fok, Kristie L. Smith, Michael Kuligowski, Bernard W. Balleine
BackgroundHigh resolution neuronal information is extraordinarily useful in understanding the brain's functionality. The development of the Golgi-Cox stain allowed observation of the neuron in its entirety with unrivalled detail. Recently tissue clearing techniques, e.g., CLARITY and CUBIC, provide the potential to observe entire neuronal circuits intact within tissue and without previous restrictions with regard to section thickness.New MethodHere we describe an improved Golgi-Cox stain method, optimized for use with CLARITY and CUBIC, that stains within 48hrs and that can be used in both fresh and fixed tissue.ResultsUsing this method, we were able to observe neurons in their entirety within a fraction of the time traditionally taken to clear tissue (48hrs). We were also able to show for the first-time that Golgi stained tissue is fluorescent when visualized using a multi-photon microscope, allowing us to image synaptic spines with a detail previously unachievable.Comparison with Existing MethodsThese novel methods provide cheap and easy to use techniques to investigate the morphology of cellular processes in the brain at a new-found depth, speed, utility and detail, without previous restrictions of time, tissue type and section thickness.ConclusionsThis is the first application of a Golgi-Cox stain to cleared brain tissue, it is investigated and discussed in detail, describing different methodologies that may be used, a comparison between the different clearing techniques and lastly the novel interaction of these techniques with this ultra-rapid stain.

Graphical abstract

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Aberrant Activation of a Gastrointestinal Transcriptional Circuit in Prostate Cancer Mediates Castration Resistance

Publication date: Available online 16 November 2017
Source:Cancer Cell
Author(s): Shipra Shukla, Joanna Cyrta, Devan A. Murphy, Edward G. Walczak, Leili Ran, Praveen Agrawal, Yuanyuan Xie, Yuedan Chen, Shangqian Wang, Yu Zhan, Dan Li, Elissa W.P. Wong, Andrea Sboner, Himisha Beltran, Juan Miguel Mosquera, Jessica Sher, Zhen Cao, John Wongvipat, Richard P. Koche, Anuradha Gopalan, Deyou Zheng, Mark A. Rubin, Howard I. Scher, Ping Chi, Yu Chen
Prostate cancer exhibits a lineage-specific dependence on androgen signaling. Castration resistance involves reactivation of androgen signaling or activation of alternative lineage programs to bypass androgen requirement. We describe an aberrant gastrointestinal-lineage transcriptome expressed in ∼5% of primary prostate cancer that is characterized by abbreviated response to androgen-deprivation therapy and in ∼30% of castration-resistant prostate cancer. This program is governed by a transcriptional circuit consisting of HNF4G and HNF1A. Cistrome and chromatin analyses revealed that HNF4G is a pioneer factor that generates and maintains enhancer landscape at gastrointestinal-lineage genes, independent of androgen-receptor signaling. In HNF4G/HNF1A-double-negative prostate cancer, exogenous expression of HNF4G at physiologic levels recapitulates the gastrointestinal transcriptome, chromatin landscape, and leads to relative castration resistance.

Teaser

Shukla et al. identify an aberrantly expressed gastrointestinal-lineage transcriptome governed by HNF4G and HNF1A in ∼30% of castration-resistant prostate cancer. HNF4G is a pioneer factor for this transcriptional program and its ectopic expression at physiologic levels reduces sensitivity to hormone deprivation.


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Stress-Activated NRF2-MDM2 Cascade Controls Neoplastic Progression in Pancreas

Publication date: Available online 16 November 2017
Source:Cancer Cell
Author(s): Jelena Todoric, Laura Antonucci, Giuseppe Di Caro, Ning Li, Xuefeng Wu, Nikki K. Lytle, Debanjan Dhar, Sourav Banerjee, Johan B. Fagman, Cecille D. Browne, Atsushi Umemura, Mark A. Valasek, Hannes Kessler, David Tarin, Michael Goggins, Tannishtha Reya, Maria Diaz-Meco, Jorge Moscat, Michael Karin
Despite expression of oncogenic KRAS, premalignant pancreatic intraepithelial neoplasia 1 (PanIN1) lesions rarely become fully malignant pancreatic ductal adenocarcinoma (PDAC). The molecular mechanisms through which established risk factors, such as chronic pancreatitis, acinar cell damage, and/or defective autophagy increase the likelihood of PDAC development are poorly understood. We show that accumulation of the autophagy substrate p62/SQSTM1 in stressed Kras^G12D acinar cells is associated with PDAC development and maintenance of malignancy in human cells and mice. p62 accumulation promotes neoplastic progression by controlling the NRF2-mediated induction of MDM2, which acts through p53-dependent and -independent mechanisms to abrogate checkpoints that prevent conversion of differentiated acinar cells to proliferative ductal progenitors. MDM2 targeting may be useful for preventing PDAC development in high-risk individuals.

Graphical abstract

Teaser

Todoric et al. demonstrate that pancreatitis-induced accumulation of the autophagy substrate p62/SQSTM1 in the context of oncogenic KRAS promotes progression to pancreatic ductal adenocarcinoma. This p62 function relies on NRF2-driven induction of MDM2 and both p53 dependent and independent activity of MDM2.


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Properties of oriented carbon fiber/polyamide 12 composite parts fabricated by fused deposition modeling

Publication date: 5 February 2018
Source:Materials & Design, Volume 139
Author(s): Guangxin Liao, Zhixiang Li, Yuchuan Cheng, Dingding Xu, Dingchun Zhu, Shenglong Jiang, Jianjun Guo, Xinde Chen, Gaojie Xu, Yuejin Zhu
This paper reports the thermal and mechanical properties of carbon fiber (CF) reinforced polyamide 12 (PA12) composites for fused deposition modeling (FDM) process. The printable filaments of carbon fiber/PA12 composites with different mass fraction were fabricated and applied in FDM. The results indicate that the tensile strength and flexural strength of 10 wt% CF/PA12 composites are enhanced by 102.2% and 251.1% respectively. The laser-flash diffusivity analysis measurements exhibit remarkable improvements on thermal conductivity (λ) of carbon fiber/PA12 composites. Moreover, the carbon fiber/PA12 composites mechanical properties are greatly improved. Our work presents a kind of anisotropic high performance composite for FDM.

Graphical abstract

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Safety of intraperitoneal Mitomycin C versus intraperitoneal oxaliplatin in patients with peritoneal carcinomatosis of colorectal cancer undergoing cytoreductive surgery and HIPEC

Publication date: Available online 15 November 2017
Source:European Journal of Surgical Oncology
Author(s): W.J. van Eden, N.F.M. Kok, K. Woensdregt, A.D.R. Huitema, H. Boot, A.G.J. Aalbers
BackgroundColorectal peritoneal carcinomatosis (PC) is commonly treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). There is an ongoing international debate about which intraperitoneal chemotherapeutic agent is preferred, Mitomycin C (MMC) or oxaliplatin. We questioned whether the type of chemotherapeutic agent influenced postoperative complication rates or short-term survival.MethodsIn this retrospective cohort study patients with colorectal PC who underwent CRS-HIPEC between January 2010 and December 2016 were included. Until March 2014 patients had preferentially been treated with MMC and thereafter with oxaliplatin in an iso-osmotic glucose/electrolyte dialysis (Dianeal®) carrier solution. Main outcomes were postoperative complications, disease free survival (DFS) and overall survival (OS). Survival analyses and multivariable analyses were performed.ResultsOne hundred four patients received MMC and 73 patients oxaliplatin. Postoperative complications did not differ between groups (44.2% (MMC) versus 43.8% (oxaliplatin); P=0.958). Median DFS was 12.5 months (IQR 6.4-32.4) in the MMC-group and 13.1 months (IQR 6.1-NA) in the oxaliplatin-group (P=0.669). Median OS was 37.2 months (IQR 17.2-NA) in the MMC-group and 29.4 months (IQR 17.0-NA) in the oxaliplatin-group (P=0.764). The type of chemotherapeutic agent did not influence OS in multivariable analysis (oxaliplatin versus MMC HR 1.09 (95%CI 0.58-2.06)). The HIPEC-phase was shorter for oxaliplatin (median 32 (IQR 31-34) versus 91 minutes (IQR 90-92) for MMC (P<0.001)).ConclusionIntraperitoneal oxaliplatin reduced the chemoperfusion time when compared to intraperitoneal MMC without adversely influencing complication rates or short-term survival. It may therefore be the preferential drug in CRS-HIPEC procedures for colorectal PC.



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Effect of different resin luting cements on the marginal fit of lithium disilicate pressed crowns

Publication date: Available online 15 November 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Radek Mounajjed, Thomas J. Salinas, Tomas Ingr, Basel Azar
Statement of problemThe vertical marginal discrepancy of restorations can increase upon cementation, and poor marginal fit can lead to cement dissolution, marginal discoloration, microleakage, and secondary caries. The amount of increase is related to the type of luting cement used, but how lithium disilicate pressed crowns are affected by different resin cements is unclear.PurposeThe purpose of this in vitro study was to compare the effect of using different resin luting cements on the vertical marginal discrepancy of lithium disilicate pressed crowns.Material and methodsA total of 18 intact extracted mandibular third molars were disinfected in a solution of 10% formalin for 7 days and were then prepared to receive a ceramic crown. Impressions were made with polyvinyl siloxane and lithium disilicate pressed crowns made and cemented with 1 of 3 resin luting cements. The marginal discrepancy was measured at 4 points on the finishing line of each tooth, with optical microscopy at ×200 magnification before and after cementation. Statistical analysis was done with the Kruskal-Wallis test to compare the median marginal increase among the 3 groups.ResultsThe least amount of marginal increase after cementation was with Harvard PremiumFlow cement, with an average marginal increase of 42 ±11 μm. RelyX Ultimate cement increased the margins by an average 45 ±29 μm. The highest marginal increase was found in the Enamel Plus HRi preheated composite resin group (116 ±47 μm).ConclusionsThe marginal increase of pressed crowns cemented with preheated composite resin (Enamel Plus HRi) exceeded the clinically acceptable range of marginal discrepancy.



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Prosthodontic rehabilitation with monolithic, multichromatic CAD-CAM complete overdentures in an adolescent patient with ectodermal dysplasia: A clinical report

Publication date: Available online 15 November 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Hussain D. Alsayed, Nasser M. Alqahtani, Yasmin M. Alzayer, Dean Morton, John A. Levon, Nadim Z. Baba
Ectodermal dysplasia is a rare, hereditary, congenital disease that affects the normal development of certain tissues and structures of ectodermal origin. The disease is manifested to different degrees of severity and may involve the nose, eyes, hair, nails, sweat glands, and enamel. This report describes a 14-year-old boy with ectodermal dysplasia, rehabilitated with monolithic, multichromatic maxillary and mandibular computer-aided design and computer-aided manufacturing (CAD-CAM) acrylic resin complete overdentures.



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