Adding Value to Milk through the Production of Cheese and Other Dairy Products on the Farm in The Netherlands

Farm Management,

Isolation and characterization of a laminin-binding protein from rat and chick muscle.

A major laminin-binding protein (LBP), distinct from previously described LBPs, has been isolated from chick and rat skeletal muscle (Mr 56,000 and 66,000, respectively). The purified LBPs from the two species were shown to be related antigenically and to have similar NH2-terminal amino acid sequences and total amino acid compositions. Protein blots using laminin and laminin fragments provided evidence that this LBP interacts with the major heparin-binding domain, E3, of laminin. Studies on the association of this LBP with muscle membrane fractions and reconstituted lipid vesicles indicate that this protein can interact with lipid bilayers and has properties of a peripheral, not an integral membrane protein. These properties are consistent with its amino acid sequence, determined from cDNAs (Clegg et al., 1988). Examination by light and electron microscopy of the LBP antigen distribution in skeletal muscle indicated that the protein is localized primarily extracellularly, near the extracellular matrix and myotube plasmalemma. While a form of this LBP has been identified in heart muscle, it is present at low or undetectable levels in other tissues examined by immunocytochemistry indicating that it is probably a muscle-specific protein. As this protein is localized extracellularly and can bind to both membranes and laminin, it may mediate myotube interactions with the extracellular matrix

Amino acid sequence and distribution of mRNA encoding a major skeletal muscle laminin binding protein: an extracellular matrix-associated protein with an unusual COOH-terminal polyaspartate domain.

Two cDNAs encoding an abundant chicken muscle extracellular matrix (ECM)-associated laminin-binding protein (LBP) have been isolated and sequenced. The predicted primary amino acid sequence includes a probable signal peptide and a site for N-linked glycosylation, but lacks a hydrophobic segment long enough to span the membrane. The COOH terminus consists of an unusual repeat of 33 consecutive aspartate residues. Comparison with other sequences indicates that this protein is different from previously described LBPs and ECM receptors. RNA blot analysis of LBP gene expression showed that LBP mRNA was abundant in skeletal and heart muscle, but barely detectable in other tissues. Blots of chicken genomic DNA suggest that a single gene encodes this LBP. The amino acid sequence and mRNA distribution are consistent with the biochemical characterization described by Hall and co-workers (Hall, D. E., K. A. Frazer, B. C. Hahn, and L. F. Reichardt. 1988. J. Cell Biol. 107:687-697). These analyses indicate that LBP is an abundant ECM-associated muscle protein with an unusually high negative charge that interacts with both membranes and laminin, and has properties of a peripheral, not integral membrane protein. Taken together, our studies show that muscle LBP is a secreted, peripheral membrane protein with an unusual polyaspartate domain. Its laminin and membrane binding properties suggest that it may help mediate muscle cell interactions with the extracellular matrix. We propose the name "aspartactin" for this LBP

Then and now: the progress in hepatitis B treatment over the past 20 years.

The ultimate goals of treating chronic hepatitis B (CHB) is prevention of hepatocellular carcinoma (HCC) and hepatic decompensation. Since the advent of effective antiviral drugs that appeared during the past two decades, considerable advances have been made not only in controlling hepatitis B virus (HBV) infection, but also in preventing and reducing the incidence of liver cirrhosis and HCC. Furthermore, several recent studies have suggested the possibility of reducing the incidence of recurrent or new HCC in patients even after they have developed HCC. Currently, six medications are available for HBV treatment including, interferon and five nucleoside/nucleotide analogues. In this review, we will examine the antiviral drugs and the progresses that have been made with antiviral treatments in the field of CHB

IQ-Pass: Access to Growth

The market of (temporary) access control is one example of an industry that is impacted by digitization and internationalisation. New possibilities come up and ask for reaction from suppliers, but require the re-specification of needs from customers as well. It is also an illustration how new regulation, in this case especially related to privacy and migration, influences industrial dynamics. Related to new technological possibilities and legislative conditions, the industry is in a process of consolidation. This case focuses on a small but innovative company, IQ-Pass, developing its growth strategy in Europe within its constellation of being a subsidiary of the regional champion Boels Rental. Students will gain an understanding of the challenges of the company, in stretching its technological leverage and customer intimacy on the one hand and expanding its sales to new (geographical) markets on the other hand

Daily enteral feeding practice on the ICU: attainment of goals and interfering factors

BACKGROUND: The purpose of this study was to evaluate the daily feeding practice of enterally fed patients in an intensive care unit (ICU) and to study the impact of preset factors in reaching predefined optimal nutritional goals. METHODS: The feeding practice of all ICU patients receiving enteral nutrition for at least 48 hours was recorded during a 1-year period. Actual intake was expressed as the percentage of the prescribed volume of formula (a success is defined as 90% or more). Prescribed volume (optimal intake) was guided by protocol but adjusted to individual patient conditions by the intensivist. The potential barriers to the success of feeding were assessed by multivariate analysis. RESULTS: Four-hundred-and-three eligible patients had a total of 3,526 records of feeding days. The desired intake was successful in 52% (1,842 of 3,526) of feeding days. The percentage of successful feeding days increased from 39% (124 of 316) on day 1 to 51% (112 of 218) on day 5. Average ideal protein intake was 54% (95% confidence interval (CI) 52 to 55), energy intake was 66% (95% CI 65 to 68) and volume 75% (95% CI 74 to 76). Factors impeding successful nutrition were the use of the feeding tube to deliver contrast, the need for prokinetic drugs, a high Therapeutic Intervention Score System category and elective admissions. CONCLUSION: The records revealed an unsatisfactory feeding process. A better use of relative successful volume intake, namely increasing the energy and protein density, could enhance the nutritional yield. Factors such as an improper use of tubes and feeding intolerance were related to failure. Meticulous recording of intake and interfering factors helps to uncover inadequacies in ICU feeding practice

Music to My Ears:The Terms ‘nona’ and ‘nyonya’ as Ethnonyms and Beyond

According to dictionaries of Standard Malay, nyonya means the married woman of a Chinese or a European, whereas nona stands for an un-married, young woman of European or Chinese descent. Hence, a dichotomous relation is reflected in the meanings for these two terms. Nowadays, nyonya almost refers exclusively to a Chinese Peranakan lady. This is the connotation of the term in Baba Malay and it is clearly visible in the ethnonym baba-nyonya or in designations of cultural areas connected to the Chinese Peranakan such as ‘baba-nyonya language’, ‘nyonya food’, ‘nyonya kuih’, or ‘nyonya clothing’. These labels coexist with other labels like ‘peranakan cuisine’ and ‘peranakan fashion’. As for nona, the word also has a different significance in the Portuguese creole varieties of Melaka (Malaysia) and Tugu (Indonesia). Parents in Portuguese Eurasians families address their daughters by the term nona, but, unlike nyonya for the Chinese Peranakans, nona is not an ethnonym for the female members of the Portuguese Eurasian communities in Indonesia, Malaysia, and Singapore. Sarkissian (1995) and Jackson (2007) analyzed the song Jinkli Nona and demonstrated that the beautiful and exotic “Portuguese” damsel - in fact, a Eurasian-African-Sinhalese “nona” - had “become synonymous over time with South and Southeast Asian women in areas influenced by Indo-Portuguese maritime contacts, both etymologically and aesthetically” (Jackson 2007: 213). In the context of Malaysia, the song is now considered a national song that is known by all ethnic groups, young and old. Expanding from there, the objective of this paper is to observe how music has influenced the meaning of the terms nyonya and nona, and to understand how the terms nyonya and nona shifted semantically between languages and nations, if that is the case. Further analysis could take into perspective pantuns and poems

The Etymology of Nyonya and Nona and their Language Contacts: Unilateral and Reciprocal Influence

Among the ethnonyms recorded for the Chinese Peranakans of Indonesia, Malaysia, and Singapore, nyonya (or nonya) stands out, because it is perceived as a loanword and its origin is strongly disputed. The Pusat Rujukan Persuratan Melayu (the main reference of the Malay language in Malaysia, containing the dictionaries Kamus Dewan and Kamus Pelajar) and the Kamus Besar Bahasa Indonesia (the main reference in Indonesia; KBBI) register nyonya. However, scholars and dilettantes in the study of the Chinese Peranakan point out to different etymologies. One of these involves the word nona, which is found in Malay, in the Melaka Creole Portuguese, and in one dictionary of Baba Malay

Optimization of Inhibitors of Mycobacterium tuberculosis Pantothenate Synthetase Based on Group Efficiency Analysis.

Ligand efficiency has proven to be a valuable concept for optimization of leads in the early stages of drug design. Taking this one step further, group efficiency (GE) evaluates the binding efficiency of each appendage of a molecule, further fine-tuning the drug design process. Here, GE analysis is used to systematically improve the potency of inhibitors of Mycobacterium tuberculosis pantothenate synthetase, an important target in tuberculosis therapy. Binding efficiencies were found to be distributed unevenly within a lead molecule derived using a fragment-based approach. Substitution of the less efficient parts of the molecule allowed systematic development of more potent compounds. This method of dissecting and analyzing different groups within a molecule offers a rational and general way of carrying out lead optimization, with potential broad application within drug discovery.Acknowledgements: This research was supported by the Bill & Melinda Gates Foundation[“Integrated Methods for TB Drug Development(IMTB)” Accelerator Grant], the UK Biotechnology and Biological Sciences Research Council (Grant BB/D006104/1), the Fundação para a Ciência e Tecnologia (PhD sponsorship to H.L.S.), and Homerton College (Junior Research Fellowship to A.C.).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/cmdc.20150041

Thr 163 Phosphorylation Causes Mcl-1 Stabilization when Degradation is Independent of the Adjacent GSK3-Targeted Phosphodegron, Promoting Drug Resistance in Cancer

The antiapoptotic Bcl-2 family member Mcl-1 is a PEST protein (containing sequences enriched in proline, glutamic acid, serine, and threonine) and is subject to rapid degradation via multiple pathways. Impaired degradation leading to the maintenance of Mcl-1 expression is an important determinant of drug resistance in cancer. Phosphorylation at Thr 163 in the PEST region, stimulated by 12-O-tetradecanoylphorbol acetic acid (TPA)-induced activation of extracellular signal-regulated kinase (ERK), is associated with Mcl-1 stabilization in BL41-3 Burkitt lymphoma cells. This contrasts with the observation that Thr 163 phosphorylation in normal fibroblasts primes glycogen synthase kinase (GSK3)-induced phosphorylation at Ser 159, producing a phosphodegron that targets Mcl-1 for degradation. In the present follow-up studies in BL41-3 cells, Mcl-1 degradation was found to be independent of the GSK3-mediated pathway, providing a parallel to emerging findings showing that Mcl-1 degradation through this pathway is lost in many different types of cancer. Findings in Mcl-1-transfected CHO cells corroborated those in BL41-3 cells in that the GSK3-targeted phosphodegron did not play a major role in Mcl-1 degradation, and a phosphomimetic T163E mutation resulted in marked Mcl-1 stabilization. TPA-treated BL41-3 cells, in addition to exhibiting Thr 163 phosphorylation and Mcl-1 stabilization, exhibited an ∼10-fold increase in resistance to multiple chemotherapeutic agents, including Ara-C, etoposide, vinblastine, or cisplatin. In these cancer cells in which Mcl-1 degradation is not dependent on the GSK3/phosphodegron-targeted pathway, ERK activation and Thr 163 phosphorylation are associated with pronounced Mcl-1 stabilization and drug resistance – effects that can be suppressed by inhibition of ERK activation