Dance A (2017) Biotechniques "PERSISTENT EPIGENETIC MEMORY."

Dance A

[Biotechniques, 2017]

Nematodes transmit environmental information, such as temperature or food availability, across generations. Amber Dance looks at how this is possible.

Munro E (2007) Cell "The microtubules dance and the spindle poles swing."

Munro E

[Cell, 2007]

Using live imaging and computer simulation, Kozlowski et al. (2007) show that an interplay between spindle pole movements, microtubule dynamics, and microtubule bending contribute to asymmetric spindle placement in the C. elegans embryo.

Barbieri, Sofia et al. (2021) International Worm Meeting "The dynamic partnered dance between PLK-1 and MEX-5: interpreting gradient formation with computational modelling."

Gotta, Monica, Barbieri, Sofia, Griffin, Erik E., Nurni Ravi, Aparna

[International Worm Meeting, 2021]

In C. elegans embryos, PLK-1 is pivotal for cell division and it orchestrates polarity establishment together with its binding partner, MEX-5. To achieve this, their localization/activity must be precisely regulated. MEX-5 enrichment at the anterior cytoplasm results from a change in its diffusivity following uneven phosphorylation along the embryo axis. We know PLK-1 relocalization to the anterior depends on MEX-5. However, the biological and physical mechanisms behind the dynamics of this protein are still poorly described. To address this, PLK-1 and MEX-5 gradient formation was measured in two CRISPR strains and significant discrepancies were revealed between the two proteins in terms of: 1) gradient steepness, as PLK-1 forms a less steep gradient compared to MEX-5; 2) dynamics, with PLK-1 gradient establishment delayed and slower; 3) diffusivity, as PLK-1 diffusion coefficient does not correspond to MEX-5's one from anterior to posterior. To shed light on PLK-1 dynamics, and how it is intertwined to MEX-5, we developed a novel Monte Carlo simulation framework able to recreate the protein motions in the C. elegans one-cell embryo. Thanks to our computational approach, we were able to postulate on the biological mechanisms behind MEX-5 and PLK-1 dynamics during the whole cell division, from early embryos to the steady-state before cytokinesis. The simulations succeed in reproducing PLK-1 gradient formation, in agreement with experimental measurements, if: 1) PLK-1 binds to phosphorylated MEX-5; 2) the binding is triggered after a defined time delay; 3) PLK-1 dynamically interacts with MEX-5, leading to a continuous replenishment of a pool of unbound PLK-1. The Monte Carlo framework we propose can eventually be applied to other polarity-related factors or mutants in which polarization is perturbed, to understand if it can be traced back to a failure in PLK-1 localization. Finally, conditions where gradient formation is altered, like after stress, can be simulated.

Dietrich CF et al. (2019) Ultrasound Int Open "Review of Dancing Parasites in Lymphatic Filariasis."

Chaubal N, Steffgen L, Mand S, Hoerauf A, Kling K, Dietrich CF, Dong Y, Piontek MS

[Ultrasound Int Open, 2019]

Lymphatic filariasis is an infection transmitted by blood-sucking mosquitoes with filarial nematodes of the species <i>Wuchereria bancrofti, Brugia malayi und B. timori</i> . It is prevalent in tropical countries throughout the world, with more than 60 million people infected and more than 1 billion living in areas with the risk of transmission. Worm larvae with a length of less than 1mm are transmitted by mosquitoes, develop in human lymphatic tissue to adult worms with a length of 7-10cm, live in the human body for up to 10 years and produce millions of microfilariae, which can be transmitted further by mosquitoes. The adult worms can be easily observed by ultrasonography because of their size and fast movements (the so-called &quot;filarial dance sign&quot;), which can be differentiated from other movements (e.g., blood in venous vessels) by their characteristic movement profile in pulsed-wave Doppler mode. Therapeutic options include (combinations of) ivermectin, albendazole, diethylcarbamazine and doxycycline. The latter depletes endosymbiotic Wolbachia bacteria from the worms and thus sterilizes and later kills the adult worms (macrofilaricidal or adulticidal effect).

Kenyon CJ et al. (1997) Cold Spring Harb Symp Quant Biol "The dance of the Hox genes: patterning the anteroposterior body axis of Caenorhabditis elegans."

Costa M, Hunter CP, Harris JM, Maloof JN, Mueller-Immergluck MM, Salser SJ, Cowing DW, Wang BB, Austin JA, Honigberg LA, Kenyon CJ, Waring DA, Wrischnik LA

[Cold Spring Harb Symp Quant Biol, 1997]

Hox mutations are fascinating. Like magic, they can turn antennae into legs or create extra wings. What makes these genes so talented? How can they make such high-level decisions? Are there simple rules that can explain the effects they have on the development of individual cells? Do the genes act multiple times during the development of a tissue to micromanage individual cell fate decisions, or can they act relatively early to initiate developmental programs that run independently of their further input?

Hengartner MO (1997) Nature "Apoptosis. CED-4 is a stranger no more."

Hengartner MO

[Nature, 1997]

The nematode worm Caenorhabditis elegans has been used with great success to identify the basic components of the machinery underlying apoptosis (programmed cell death). Indeed, of the three key cell death genes that have been identified in C. elegans, two - ced-3 and ced-9 - have mammalian homologues that also function in apoptosis. But the sequence of the third gene, ced-4, revealed no obvious mammalian homologue, and precious little in terms of possible mechanism of action. A flurry of activity has changed that. A paper by Zou et al., published earlier this month in Cell, provides a homologue. And work by Chinnaiyan et al. (page 728 of this issue) and by Seshagiri and Miller in Current Biology lays down some choreography for the part that CED-4 protein plays in the molecular dance of death.

Rohozkova J et al. (2019) Nucleus "Pairing of homologous chromosomes in C. elegans meiosis requires DEB-1 - an orthologue of mammalian vinculin."

Fukalova J, Rohozkova J, Flachs P, Hlkova L, Hozak P

[Nucleus, 2019]

During meiosis, homologous chromosomes undergo a dramatic movement in order to correctly align. This is a critical meiotic event but the molecular properties of this 'chromosomal dance' still remainunclear. We identified DEB-1 - an orthologue of mammalian vinculin - as a new component of the mechanistic modules responsible for attaching the chromosomes to the nuclear envelope as apart of the LINC complex. In early meiotic nuclei of C. elegans, DEB-1 is localized to the nuclear periphery and alongside the synaptonemal complex of paired homologues. Upon DEB-1 depletion, chromosomes attached to SUN-1 foci remain highly motile until late pachytene. Although the initiation of homologue pairing started normally, irregularities in the formation of the synaptonemal complex occur, and these results in meiotic defects such as increased number of univalents at diakinesis and high embryonic lethality. Our data identify DEB-1 as a new player regulating chromosome dynamics and pairing during meiotic prophase I.

Shenoy RK et al. (2007) Ann Trop Med Parasitol "Doppler ultrasonography reveals adult-worm nests in the lymph vessels of children with brugian filariasis."

Shenoy RK, Suma TK, Ramesh C, Padma S, Abhilash G, Rahmah N, Kumaraswami V

[Ann Trop Med Parasitol, 2007]

Although ultrasonography has allowed 'nests' of live adult worms and dilated lymphatics to be detected in the early stages of infection with Wuchereria bancrofti, previous attempts to locate such adult-worm nests in brugian filariasis have been unsuccessful. In this study, the successful location of live adult Brugia malayi parasites, in the lymphatics of the axilla, thigh, epitrochlear region and/or popliteal fossa of children aged 3-15 years, is described for the first time. The 'filarial dance sign' (FDS), which indicates the presence of live adult worms, was observed in six children with microfilaraemia and in eight children who, though amicrofilaraemic, either had experienced an episode of lymphoedema (one) or were only positive for antifilarial IgG4 antibodies (seven). In bancroftian infection, the adult-worm nests have mostly been seen in asymptomatic but microfilaraemic subjects. The suspected worm nests, 18 in the 14 children, were all confirmed using colour-power and pulse-wave Doppler examinations. The worm nests were distinctly smaller and the wriggling movements were less rapid and less conspicuous than those seen in bancroftian filariasis. The importance of these findings in the management and control of lymphatic filariasis is discussed.

Shenoy RK et al. (2000) Ann Trop Med Parasitol "Apparent failure of ultrasonography to detect adult worms of Brugia malayi."

Kumaraswami V, John A, Shenoy RK, Hameed S, Suma TK

[Ann Trop Med Parasitol, 2000]

Adult worms of Wuchereria bancrofti, or rather their characteristic movements (the 'filarial dance'), can now be detected in the scrotal lymphatics of microfilaraemic males, using ultrasonography. This ability has been used to delineate the lymphatic pathology of bancroftian filariasis, guide the surgical removal of the adult worms and, most importantly, assess the macrofilaricidal effects of antifilarial drugs. In the present study, the first report of the use of ultrasonography in brugian filariasis, 22 men (aged 18-62 years) with 60-2972 (median = 370) Brugia malayi microfilariae/ml blood were subjected to ultrasonography using a linear, 7.5-MHz probe. In addition, four other men (aged 19-35 years), with W. bancrofti microfilaraemia [28-524 (median = 234) microfilariae/ml], were similarly examined. Adult worms were not detectable in any of the patients with B. malayi parasitaemia but were detected in the scrotal lymphatics of two of the four individuals with W. bancrofti infection. The reasons for the failure to detect adult B. malayi and the limitations of ultrasound as a screening tool are examined. The results highlight the differences between the two species that cause most lymphatic filariasis and the need for rapid development of tools that can be used for the control of brugian lymphatic filariasis.

Shenoy RK et al. (2009) J Commun Dis "Relevance of anti-BmR1 IgG4 antibodies in children from an area endemic for Brugia malayi infection in Kerala, India."

Thaslim AX, Suma TK, Shenoy RK, Rahmah N, Gopu RB, Kumaraswami V

[J Commun Dis, 2009]

Brugian filariasis prevalent mostly in South-East Asian countries including India contributes to a small but significant proportion of the socioeconomic burden due to lymphatic filariasis. Along with bancroftian filariasis, brugian filariasis has been targeted for elimination globally. The lack of a reliable daytime diagnostic test has been seen as an important barrier to the successful implementation and monitoring of elimination programmes in brugia endemic areas. We evaluated an anti-BmRI-IgG4 antibody test namely, 'Brugia Rapid' in a large study meant to understand the clinical and pathological manifestations of brugian filariasis in children. We found the test superior to traditional night blood screening for microfilaraemia. Although an antibody detection test, we found it to be a reliable indicator of brugian infection. Among the 100 children studied extensively, 94% of the microfilaraemics, 86% of those showing filarial dance sign indicating presence of, live adult worms and 78% having abnormal lymphatics on lymphoscintigraphy were IgG4 positive. Coupled with its advantages like ease of use any time of the day, high sensitivity and specificity, this test may be the ideal tool to assist programme managers in their efforts to eliminate lymphatic filariasis where brugian infections are found.