Algorithmic and Hardness Results for the Colorful Components Problems

In this paper we investigate the colorful components framework, motivated by applications emerging from comparative genomics. The general goal is to remove a collection of edges from an undirected vertex-colored graph $G$ such that in the resulting graph $G'$ all the connected components are colorful (i.e., any two vertices of the same color belong to different connected components). We want $G'$ to optimize an objective function, the selection of this function being specific to each problem in the framework. We analyze three objective functions, and thus, three different problems, which are believed to be relevant for the biological applications: minimizing the number of singleton vertices, maximizing the number of edges in the transitive closure, and minimizing the number of connected components. Our main result is a polynomial time algorithm for the first problem. This result disproves the conjecture of Zheng et al. that the problem is $NP$-hard (assuming $P \neq NP$). Then, we show that the second problem is $APX$-hard, thus proving and strengthening the conjecture of Zheng et al. that the problem is $NP$-hard. Finally, we show that the third problem does not admit polynomial time approximation within a factor of $|V|^{1/14 - \epsilon}$ for any $\epsilon > 0$, assuming $P \neq NP$ (or within a factor of $|V|^{1/2 - \epsilon}$, assuming $ZPP \neq NP$).Comment: 18 pages, 3 figure

Male Infertility is a Women\u27s Health Issue-Research and Clinical Evaluation of Male Infertility Is Needed

Infertility is a devastating experience for both partners as they try to conceive. Historically, when a couple could not conceive, the woman has carried the stigma of infertility; however, men and women are just as likely to contribute to the couple\u27s infertility. With the development of assisted reproductive technology (ART), the treatment burden for male and unexplained infertility has fallen mainly on women. Equalizing this burden requires reviving research on male infertility to both improve treatment options and enable natural conception. Despite many scientific efforts, infertility in men due to sperm dysfunction is mainly diagnosed by a semen analysis. The semen analysis is limited as it only examines general sperm properties such as concentration, motility, and morphology. A diagnosis of male infertility rarely includes an assessment of internal sperm components such as DNA, which is well documented to have an impact on infertility, or other components such as RNA and centrioles, which are beginning to be adopted. Assessment of these components is not typically included in current diagnostic testing because available treatments are limited. Recent research has expanded our understanding of sperm biology and suggests that these components may also contribute to the failure to achieve pregnancy. Understanding the sperm\u27s internal components, and how they contribute to male infertility, would provide avenues for new therapies that are based on treating men directly for male infertility, which may enable less invasive treatments and even natural conception

Tubulin nucleotide status controls Sas-4-dependent pericentriolar material recruitment

Regulated centrosome biogenesis is required for accurate cell division and for maintaining genome integrity1. Centrosomes consist of a centriole pair surrounded by a protein network known as pericentriolar material (PCM)1. PCM assembly is a tightly regulated, critical step that determines a centrosome’s size and capability2–4. Here, we report a role for tubulin in regulating PCM recruitment via the conserved centrosomal protein Sas-4. Tubulin directly binds to Sas-4; together they are components of cytoplasmic complexes of centrosomal proteins5,6. A Sas-4 mutant, which cannot bind tubulin, enhances centrosomal protein complex formation and has abnormally large centrosomes with excessive activity. These suggest that tubulin negatively regulates PCM recruitment. Whereas tubulin-GTP prevents Sas-4 from forming protein complexes, tubulin-GDP promotes it. Thus, tubulin’s regulation of PCM recruitment depends on its GTP/GDP-bound state. These results identify a role for tubulin in regulating PCM recruitment independent of its well-known role as a building block of microtubules7. Based on its guanine bound state, tubulin can act as a molecular switch in PCM recruitment

Plk1/Polo Phosphorylates Sas-4 at the Onset of Mitosis for an Efficient Recruitment of Pericentriolar Material to Centrosomes

Centrosomes are the major microtubule-organizing centers, consisting of centrioles surrounded by a pericentriolar material (PCM). Centrosomal PCM is spatiotemporally regulated to be minimal during interphase and expands as cells enter mitosis. It is unclear how PCM expansion is initiated at the onset of mitosis. Here, we identify that, in Drosophila, Plk1/Polo kinase phosphorylates the conserved centrosomal protein Sas-4 in vitro. This phosphorylation appears to occur at the onset of mitosis, enabling Sas-4's localization to expand outward from meiotic and mitotic centrosomes. The Plk1/Polo kinase site of Sas-4 is then required for an efficient recruitment of Cnn and gamma-tubulin, bona fide PCM proteins that are essential for PCM expansion and centrosome maturation. Point mutations at Plk1/Polo sites of Sas-4 affect neither centrosome structure nor centriole duplication but specifically reduce the affinity to bind Cnn and gamma-tubulin. These observations identify Plk1/Polo kinase regulation of Sas-4 as essential for efficient PCM expansion

Sperm centriole assessment identifies male factor infertility in couples with unexplained infertility - a pilot study

Unexplained infertility affects about one-third of infertile couples and is defined as the failure to identify the cause of infertility despite extensive evaluation of the male and female partners. Therefore, there is a need for a multiparametric approach to study sperm function. Recently, we developed a Fluorescence-Based Ratiometric Analysis of Sperm Centrioles (FRAC) assay to determine sperm centriole quality. Here, we perform a pilot study of sperm from 10 fertile men and 10 men in couples with unexplained infertility, using three centriolar biomarkers measured at three sperm locations from two sperm fractions, representing high and low sperm quality. We found that FRAC can identify men from couples with unexplained infertility as the likely source of infertility. Higher quality fractions from 10 fertile individuals were the reference population. All 180 studied FRAC values in the 10 fertile individuals fell within the reference population range. Eleven of the 180 studied FRAC values in the 10 infertile patients were outliers beyond the 95% confidence intervals (P = 0.0008). Three men with unexplained infertility had outlier FRAC values in their higher quality sperm fraction, while four had outlier FRAC values in their lower quality sperm fraction (3/10 and 4/10, P = 0.060 and P = 0.025, respectively), suggesting that these four individuals are infertile due, in part, to centriolar defects. We propose that a larger scale study should be performed to determine the ability of FRAC to identify male factor infertility and its potential contribution to sperm multiparametric analysis

Mediation of adenylyl cyclase sensitization by PTX-insensitive Gα oA , Gα i1 , Gα i2 or Gα i3

Chronic activation of mu-opioid receptors, which couple to pertussis toxin-sensitive Gα i/o proteins to inhibit adenylyl cyclase (AC), leads to a compensatory sensitization of AC. Pertussis toxin-insensitive mutations of Gα i/o subtypes, in which the pertussis toxin-sensitive cysteine is mutated to isoleucine (G ), were used to determine whether each of the Gα i/o subtypes is able to mediate sensitization of AC. G , G , G or G were individually transiently transfected into C6 glioma cells stably expressing the mu-opioid receptor, or transiently co-expressed with the mu-opioid receptor into human embryonic kidney (HEK)293T cells. Cells were treated with pertussis toxin to uncouple endogenous Gα i/o proteins, followed by acute or chronic treatment with the mu-opioid agonist, [D-Ala 2 ,N-Me-Phe 4 ,Gly 5 -ol]enkephalin (DAMGO). Each Gα i/o subtype mediated acute DAMGO inhibition of AC and DAMGO-induced sensitization of AC. The potency for DAMGO to stimulate sensitization was independent of the Gα i/o subtype, but the level of sensitization was increased in clones expressing higher levels of Gα i/o subunits. Sensitization of AC mediated by a component of fetal bovine serum, which was also dependent on the level of functional Gα i/o subunits in the cell, was observed. This serum-mediated sensitization partially masked mu-opioid-mediated sensitization when expressed as percentage overshoot due to an apparent increase in AC activity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65707/1/j.1471-4159.2006.04176.x.pd

Algorithms for Cut Problems on Trees

We study the {\sc multicut on trees} and the {\sc generalized multiway Cut on trees} problems. For the {\sc multicut on trees} problem, we present a parameterized algorithm that runs in time $O^{*}(\rho^k)$, where $\rho = \sqrt{\sqrt{2} + 1} \approx 1.555$ is the positive root of the polynomial $x^4-2x^2-1$. This improves the current-best algorithm of Chen et al. that runs in time $O^{*}(1.619^k)$. For the {\sc generalized multiway cut on trees} problem, we show that this problem is solvable in polynomial time if the number of terminal sets is fixed; this answers an open question posed in a recent paper by Liu and Zhang. By reducing the {\sc generalized multiway cut on trees} problem to the {\sc multicut on trees} problem, our results give a parameterized algorithm that solves the {\sc generalized multiway cut on trees} problem in time $O^{*}(\rho^k)$, where $\rho = \sqrt{\sqrt{2} + 1} \approx 1.555$ time

Angiomatoid giant cellular blue nevus of vaginal wall associated with pregnancy

<p>Abstract</p> <p>Background</p> <p>Blue nevi that arise from the Müllerian tract are rare melanocytic lesions. Several histopathologic variants of cellular blue nevi have been described. The angiomatoid variant is characterized by a vascular component, and is considered to be a rare variant. Few studies have explored the influence of pregnancy on melanocytic lesions.</p> <p>Case</p> <p>A 29-year-old woman was presented with a pigmented vaginal lesion that increased gradually during pregnancy. A full term gynecologic examination showed a tumor mass protruding into the vaginal canal. The mass was resected during cesarean-section under the clinical impression of vaginal hemangioma.</p> <p>Result</p> <p>Gross examination revealed a cystic mass measuring 6.0 × 4.3 × 3.5 cm, which was filled with dark friable material. Histologically, the mass showed a subepithelial cellular proliferation of heavily pigmented dendritic melanocytes with prominent vascular stroma. Cytologic pleomorphism, junctional activity, atypical mitosis, and necrosis were not found. The proliferation was immunoreactive for HMB-45, S-100 and melan-A, and non-immunoreactive for CD34, smooth muscle actin, and AE1/AE3. The MIB-1 proliferative index was less than 1%. The patient had a postoperative course without complication.</p> <p>Conclusions</p> <p>Angiomatoid giant cellular blue nevus arising from the vagina during pregnancy is extremely rare. The low proliferative index and absence of cytologic pleomorphism, or necrosis, supports a benign biological behavior. Clinical follow-up showed no evidence of recurrence at one year after the resection of the mass.</p

Candidatus Bartonella mayotimonensis and Endocarditis

We describe a new Bartonella species for which we propose the name Candidatus Bartonella mayotimonensis. It was isolated from native aortic valve tissue of a person with infective endocarditis. The new species was identified by using PCR amplification and sequencing of 5 genes (16S rRNA gene, ftsZ, rpoB, gltA, and internal transcribed spacer region)