A trans-acting cyclase off-loading strategy for non-ribosomal peptide synthetases

The terminal step in the biosynthesis of nonribosomal peptides is the hydrolytic release and, frequently, macrocyclization of an aminoacyl-S-thioester by an embedded thioesterase. The surugamide biosynthetic pathway is composed of two nonribosomal peptide synthetase (NRPS) assembly lines in which one produces surugamide A, which is a cyclic octapeptide, and the other produces surugamide F, a linear decapeptide. The terminal module of each system lacks an embedded thioesterase, which led us to question how the peptides are released from the assembly line (and cyclized in the case of surugamide A). We characterized a cyclase belonging to the β-lactamase superfamily in vivo, established that it is a trans-acting release factor for both compounds, and verified this functionality in vitro with a thioester mimic of linear surugamide A. Using bioinformatics, we estimate that ∼11% of filamentous Actinobacteria harbor an NRPS system lacking an embedded thioesterase and instead employ a trans-acting cyclase. This study improves the paradigmatic understanding of how nonribosomal peptides are released from the terminal peptidyl carrier protein and adds a new dimension to the synthetic biology toolkit

A chromatogram-simplified Streptomyces albus host for heterologous production of natural products

Cloning natural product biosynthetic gene clusters from cultured or uncultured sources and their subsequent expression by genetically tractable heterologous hosts is an essential strategy for the elucidation and characterisation of novel microbial natural products. The availability of suitable expression hosts is a critical aspect of this workflow. In this work, we mutagenised five endogenous biosynthetic gene clusters from Streptomyces albus S4, which reduced the complexity of chemical extracts generated from the strain and eliminated antifungal and antibacterial bioactivity. We showed that the resulting quintuple mutant can express foreign biosynthetic gene clusters by heterologously producing actinorhodin, cinnamycin and prunustatin. We envisage that our strain will be a useful addition to the growing suite of heterologous expression hosts available for exploring microbial secondary metabolism

Longest property-preserved common factor

In this paper we introduce a new family of string processing problems. We are given two or more strings and we are asked to compute a factor common to all strings that preserves a specific property and has maximal length. Here we consider two fundamental string properties: square-free factors and periodic factors under two different settings, one per property. In the first setting, we are given a string x and we are asked to construct a data structure over x answering the following type of on-line queries: given string y, find a longest square-free factor common to x and y. In the second setting, we are given k strings and an integer 1 < k’ ≤ k and we are asked to find a longest periodic factor common to at least k’ strings. We present linear-time solutions for both settings. We anticipate that our paradigm can be extended to other string properties

Nutrient intakes of rural Tibetan mothers: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Tibetan food intake is influenced by the region's high altitude and unique culture. Few published studies of nutrient intakes among Tibetan women are available. The present study of Tibetan mothers with young children explores dietary patterns, nutrient intakes, and differences between socio-demographic groups.</p> <p>Methods</p> <p>A cross-sectional survey of 386 women with a child aged less than 24 months was conducted in rural areas surrounding Lhasa, Tibet. All participants were recruited using simple random sampling and were interviewed face-to-face by trained investigators. Dietary information was collected via a food frequency questionnaire. Nutrient intakes were calculated using food composition tables. Non-parametric tests were used to compare nutrient intakes according to socio-demographic variables, and to compare results with the <it>2002 Chinese National Nutrition and Health Survey </it>(2002 NNHS) and dietary reference intakes (DRIs).</p> <p>Results</p> <p>Median intakes of energy (<it>p </it>< 0.001), protein (<it>p </it>< 0.001), fat (<it>p </it>< 0.001), vitamin A (<it>p </it>< 0.001), vitamin B1 (<it>p </it>< 0.001), vitamin B2 (<it>p </it>< 0.001), vitamin C (<it>p </it>< 0.001), and vitamin E (<it>p </it>< 0.001) were lower than the average levels reported in 2002 NNHS. The median intakes of calcium (517 mg/d, <it>p </it>< 0.001), iron (35 mg/d, <it>p </it>< 0.001), and zinc (17.3 mg/d, <it>p </it>< 0.001) were higher than the average levels in 2002 NNHS. The highest education subgroup had significantly higher intakes of vitamins A and C than the lowest education subgroup.</p> <p>Conclusion</p> <p>Although the diet of Tibetan mothers with young children has been partially influenced by other factors, their dietary patterns are still mostly composed of Tibetan traditional foods. Compared with the 2002 NNHS, Tibetan women with young children appear to have insufficient intakes of many nutrients, which will affect their nutritional status.</p

Low anemia prevalence in school-aged children in Bangalore, South India: possible effect of school health initiatives

Objective: Anemia is a serious public health problem in Indian school children. Since 2003, simple health intervention programs such as antihelminthic treatment and vitamin A supplementation have been implemented in primary schools in the Bangalore region, Karnataka, India. This study examines the prevalence of anemia in school children who are beneficiaries of this program. Design: Cross-sectional survey. Setting: Bangalore district, South India. Subjects: A total of 2030 boys and girls, aged 5-15 years, attending schools in the Bangalore district. Interventions: School-based, twice yearly intervention: deworming (albendazole 400mg, single oral dose) and vitamin A supplementation (200 000 ¿U, single oral dose). Main outcome measures: Anemia prevalence based on measure of blood hemoglobin (Hb). Results: Mean age and blood Hb concentration of all children were 9.5±2.6 years and 12.6±1.1 g/dl (range 5.6-16.7), respectively. The overall anemia prevalence in this group was 13.6%. Anemia prevalence was lower in boys than girls (12.0%; n=1037 vs 15.3%; n = 993 respectively,

Algorithmic Framework For Approximate Matching Under Bounded Edits With Applications To Sequence Analysis

We present a novel algorithmic framework for solving approximate sequence matching problems that permit a bounded total number k of mismatches, insertions, and deletions. The core of the framework relies on transforming an approximate matching problem into a corresponding exact matching problem on suitably edited string suffixes, while carefully controlling the required number of such edited suffixes to enable the design of efficient algorithms. For a total input size of n, our framework limits the number of generated edited suffixes to no more than a factor of O(log kn) of the input size (for any constant k), and restricts the algorithm to linear space usage by overlapping the generation and processing of edited suffixes. Our framework improves the best known upper bound of n2k1.5/2Ω(logn/k) for the classic k-edit longest common substring problem [Abboud, Williams, and Yu; SODA 2015] to yield the first strictly sub-quadratic time algorithm that runs in O(nlog kn) time and O(n) space for any constant k. We present similar subquadratic time and linear space algorithms for (i) computing the alignment-free distance between two genomes based on the k-edit average common substring measure, (ii) mapping reads/read fragments to a reference genome while allowing up to k edits, and (iii) computing all-pair maximal k-edit common substrings (also, suffix/prefix overlaps), which has applications in clustering and assembly. We expect our algorithmic framework to be a broadly applicable theoretical tool, and may inspire the design of practical heuristics and software

Linear-Space Data Structures for Range Frequency Queries on Arrays and Trees

Abstract. We present O(n)-space data structures to support various range frequency queries on a given array A[0: n − 1] or tree T with n nodes. Given a query consisting of an arbitrary pair of pre-order rank in-dices (i, j), our data structures return a least frequent element, mode, or α-minority of the multiset of elements in the unique path with endpoints at indices i and j in A or T. We describe a data structure that sup-ports range least frequent element queries on arrays in O( n/w) time, improving the Θ( n) worst-case time required by the data structure of Chan et al. (SWAT 2012), where w ∈ Ω(logn) is the word size in bits. We describe a data structure that supports range mode queries on trees in O(log log n n/w) time, improving the Θ( n logn) worst-case time required by the data structure of Krizanc et al. (ISAAC 2003). Finally, we describe a data structure that supports range α-minority queries on trees in O(α−1 log log n) time, where α ∈ [0, 1] can be specified at query time.