Incorporation of Pentraxin 3 into Hyaluronan Matrices Is Tightly Regulated and Promotes Matrix Cross-linking

Mammalian oocytes are surrounded by a highly hydrated hyaluronan (HA)-rich extracellular matrix with embedded cumulus cells, forming the cumulus cell·oocyte complex (COC) matrix. The correct assembly, stability, and mechanical properties of this matrix, which are crucial for successful ovulation, transport of the COC to the oviduct, and its fertilization, depend on the interaction between HA and specific HA-organizing proteins. Although the proteins inter-α-inhibitor (IαI), pentraxin 3 (PTX3), and TNF-stimulated gene-6 (TSG-6) have been identified as being critical for COC matrix formation, its supramolecular organization and the molecular mechanism of COC matrix stabilization remain unknown. Here we used films of end-grafted HA as a model system to investigate the molecular interactions involved in the formation and stabilization of HA matrices containing TSG-6, IαI, and PTX3. We found that PTX3 binds neither to HA alone nor to HA films containing TSG-6. This long pentraxin also failed to bind to products of the interaction between IαI, TSG-6, and HA, among which are the covalent heavy chain (HC)·HA and HC·TSG-6 complexes, despite the fact that both IαI and TSG-6 are ligands of PTX3. Interestingly, prior encounter with IαI was required for effective incorporation of PTX3 into TSG-6-loaded HA films. Moreover, we demonstrated that this ternary protein mixture made of IαI, PTX3, and TSG-6 is sufficient to promote formation of a stable (i.e. cross-linked) yet highly hydrated HA matrix. We propose that this mechanism is essential for correct assembly of the COC matrix and may also have general implications in other inflammatory processes that are associated with HA cross-linking

Melioidosis with a subdural collection – a case report

Abstract Background Melioidosis is an infection caused by Burkholderia pseudomallei, which is more prevalent in the tropics and leads to significant morbidity and mortality. It characteristically produces widespread caseous lesions and abscesses, and can present with varied clinical manifestations. Melioidosis involving the central nervous system is uncommon. Case presentation A 42-year-old Sri Lankan male with type 2 diabetes presented with a febrile illness of 6 days with headache and constitutional symptoms. Clinical examination was unremarkable. Four days later, he developed focal seizures involving the left leg and numbness of the left side. Initial laboratory investigations were suggestive of a bacterial infection. Blood culture was reported as positive for a Pseudomonas species, which was resistant to gentamicin. Contrast enhanced CT and MRI scans of the brain showed a subdural collection in the right fronto-temporo-parietal region with possible abscess formation. Melioidosis antibody testing using indirect hemagglutination method was reactive with a titre more than 1/10,240. He was treated with intravenous meropenem and oral co-trimoxazole for 8 weeks (Intensive phase). The subdural collection was managed conservatively, and seizures were treated with oral antiepileptics. At 7 weeks, follow-up contrast enhanced MRI showed improvement of the subdural collection, and inflammatory markers had normalized. He was discharged after 8 weeks, and treated with oral co-trimoxazole and doxycycline for 6 months (eradication phase). At 6 months follow-up, the patient is asymptomatic. Conclusions Cerebral melioidosis is an unusual presentation of melioidosis where the diagnosis can be easily missed. Knowledge of the protean manifestations of melioidosis is of paramount importance in order to detect and treat this potentially fatal infection appropriately, especially in tropical countries where the disease is endemic

Inter-α-inhibitor impairs TSG-6-induced hyaluronan cross-linking

Under inflammatory conditions and in the matrix of the cumulus-oocyte complex, the polysaccharide hyaluronan (HA) becomes decorated covalently with heavy chains (HCs) of the serum glycoprotein inter-α-inhibitor (IαI). This alters the functional properties of the HA as well as its structural role within extracellular matrices. The covalent transfer of HCs from IαI to HA is catalyzed by TSG-6 (tumor necrosis factor-stimulated gene-6), but TSG-6 is also known as a HA cross-linker that induces condensation of the HA matrix. Here, we investigate the interplay of these two distinct functions of TSG-6 by studying the ternary interactions of IαI and TSG-6 with well defined films of end-grafted HA chains. We demonstrate that TSG-6-mediated cross-linking of HA films is impaired in the presence of IαI and that this effect suppresses the TSG-6-mediated enhancement of HA binding to CD44-positive cells. Furthermore, we find that the interaction of TSG-6 and IαI in the presence of HA gives rise to two types of complexes that independently promote the covalent transfer of heavy chains to HA. One type of complex interacts very weakly with HA and is likely to correspond to the previously reported covalent HC·TSG-6 complexes. The other type of complex is novel and binds stably but noncovalently to HA. Prolonged incubation with TSG-6 and IαI leads to HA films that contain, in addition to covalently HA-bound HCs, several tightly but noncovalently bound molecular species. These findings have important implications for understanding how the biological activities of TSG-6 are regulated, such that the presence or absence of IαI will dictate its function

\u3cem\u3eMoby Dick\u3c/em\u3e Pointed West

Third-generation dorymen, brothers Mark Lichtenthaler (at the helm) and Brett Lichtenthaler (pusher), launch the Moby Dick.https://digitalcommons.linfield.edu/dory_archphotos_all/1004/thumbnail.jp

A hybrid contact state analysis methodology for robotic-based adjustment of cylindrical pair

The peg-in-hole insertion and adjustment operation is one of the most common tasks in the robotic and automatic assembly processes. Fine motion strategies associated with adjustment operations on a peg-in-hole are fundamental manipulations that can be utilised in dynamic assembly and reconfigurable workholding or fixturing systems. This paper presents a comprehensive study of robotic-based height adjustment of a cylindrical pair based on maintaining minimum contact forces between the links

Globalization, policy reforms and productivity growth in developing countries: evidence from Sri Lanka

Sri Lanka's economic policy strategies radically moved away from inward-looking import-substituting industrialization to outward-looking export-oriented industrialization (EOI) in 1977. The EOI strategy was implemented through a broad agenda of reforms including trade liberalization, privatization of state owned enterprises and financial deregulation. These reforms had a profound impact on productivity in the export oriented production sector (primarily manufacturing) and laid the foundation for rapid growth and structural change. This study empirically analyzes the impact of policy reforms on the total factor productivity (TFP) of manufacturing industries in Sri Lanka. A balanced panel data set of all 27 manufacturing industries over 21 years is used. The industry heterogeneity effects are taken into account through the validation of a fixed effects model. The empirical results confirm, in general, that post 1977 pursuit of the EOI strategy has resulted in TFP growth. However, in an uncertain investment and economic climate due to the ethnic conflict that has engulfed Sri Lanka, TFP growth has reversed dramatically since 1994. The findings reinforce the view that in order to increase productivity and growth in developing countries in this era of Globalization the pursuit of open economy policies alone is insufficient. Fostering of a stable political environment is also necessary

Dhana Labha: A financial management application to underbanked communities in Rural Sri Lanka

This paper presents findings from field trial of a mobile application called ‘Dhana Labha’ in a rural Sri Lankan community. Dhana Labha was designed to be used by the community members to manage their personal finances, oversee their performance in managing multiple microfinance loans and assist in loan collection. We distributed the application among thirty eight microfinance clients and studied their use over a period of six months. Our findings show that the use of Dhana Labha had a positive impact on existing local practices and financial awareness while prompting the participants to develop unexpected new practices around microfinance workflows. Our findings highlight the importance of understanding existing sociocultural practices for designing applications, as they strongly affect and shape the use of technology in a constrained setting