Averting biodiversity collapse in tropical forest protected areas

The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon¹⁻³. With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses⁴⁻⁹. As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world’s major tropical regions. Our analysis reveals great variation in reserve ‘health’: about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.Keywords: Ecology, Environmental scienc

An Instrumented Minimally Invasive Surgical Tool: Design and Calibration

Minimally invasive surgical procedures have improved the standard of patient care by reducing recovery time, chance of infection, and scarring. A recent review estimates that leaks occur in 3% to 6% of bowel anastomoses, resulting in “increased morbidity and mortality and adversely [affecting] length of stay, cost, and cancer recurrence” [23]. Many of these leaks are caused by poor handling and ischemic tissue

Seminal Plasma-Derived Extracellular-Vesicle Fractions from HIV-Infected Men Exhibit Unique MicroRNA Signatures and Induce a Proinflammatory Response in Cells Isolated from the Female Reproductive Tract.

The continuing spread of HIV/AIDS is predominantly fueled by sexual exposure to HIV-contaminated semen. Seminal plasma (SP), the liquid portion of semen, harbors a variety of factors that may favor HIV transmission by facilitating viral entry into host cells, eliciting the production of proinflammatory cytokines, and enhancing the translocation of HIV across the genital epithelium. One important and abundant class of factors in SP is extracellular vesicles (EVs), which, in general, are important intercellular signal transducers. Although numerous studies have characterized blood plasma-derived EVs from both uninfected and HIV-infected individuals, little is known about the properties of EVs from the semen of HIV-infected individuals. We report here that fractionated SP enriched for EVs from HIV-infected men induces potent transcriptional responses in epithelial and stromal cells that interface with the luminal contents of the female reproductive tract. Semen EV fractions from acutely infected individuals induced a more proinflammatory signature than those from uninfected individuals. This was not associated with any observable differences in the surface phenotypes of the vesicles. However, microRNA (miRNA) expression profiling analysis revealed that EV fractions from infected individuals exhibit a broader and more diverse profile than those from uninfected individuals. Taken together, our data suggest that SP EVs from HIV-infected individuals exhibit unique miRNA signatures and exert potent proinflammatory transcriptional changes in cells of the female reproductive tract, which may facilitate HIV transmission.IMPORTANCE Seminal plasma (SP), the major vehicle for HIV, can modulate HIV transmission risk through a variety of mechanisms. Extracellular vesicles (EVs) are extremely abundant in semen, and because they play a key role in intercellular communication pathways and immune regulation, they may impact the likelihood of HIV transmission. However, little is known about the properties and signaling effects of SP-derived EVs in the context of HIV transmission. Here, we conduct a phenotypic, transcriptomic, and functional characterization of SP and SP-derived EVs from uninfected and HIV-infected men. We find that both SP and its associated EVs elicit potent proinflammatory transcriptional responses in cells that line the genital tract. EVs from HIV-infected men exhibit a more diverse repertoire of miRNAs than EVs from uninfected men. Our findings suggest that EVs from the semen of HIV-infected men may significantly impact the likelihood of HIV transmission through multiple mechanisms

Seminal plasma promotes decidualization of endometrial stromal fibroblasts in vitro from women with and without inflammatory disorders in a manner dependent on interleukin-11 signaling.

Study questionDo seminal plasma (SP) and its constituents affect the decidualization capacity and transcriptome of human primary endometrial stromal fibroblasts (eSFs)?Summary answerSP promotes decidualization of eSFs from women with and without inflammatory disorders (polycystic ovary syndrome (PCOS), endometriosis) in a manner that is not mediated through semen amyloids and that is associated with a potent transcriptional response, including the induction of interleukin (IL)-11, a cytokine important for SP-induced decidualization.What is known alreadyClinical studies have suggested that SP can promote implantation, and studies in vitro have demonstrated that SP can promote decidualization, a steroid hormone-driven program of eSF differentiation that is essential for embryo implantation and that is compromised in women with the inflammatory disorders PCOS and endometriosis.Study design, size, durationThis is a cross-sectional study involving samples treated with vehicle alone versus treatment with SP or SP constituents. SP was tested for the ability to promote decidualization in vitro in eSFs from women with or without PCOS or endometriosis (n = 9). The role of semen amyloids and fractionated SP in mediating this effect and in eliciting transcriptional changes in eSFs was then studied. Finally, the role of IL-11, a cytokine with a key role in implantation and decidualization, was assessed as a mediator of the SP-facilitated decidualization.Participants/materials, setting, methodseSFs and endometrial epithelial cells (eECs) were isolated from endometrial biopsies from women of reproductive age undergoing benign gynecologic procedures and maintained in vitro. Assays were conducted to assess whether the treatment of eSFs with SP or SP constituents affects the rate and extent of decidualization in women with and without inflammatory disorders. To characterize the response of the endometrium to SP and SP constituents, RNA was isolated from treated eSFs or eECs and analyzed by RNA sequencing (RNAseq). Secreted factors in conditioned media from treated cells were analyzed by Luminex and ELISA. The role of IL-11 in SP-induced decidualization was assessed through Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas-9-mediated knockout experiments in primary eSFs.Main results and the role of chanceSP promoted decidualization both in the absence and presence of steroid hormones (P < 0.05 versus vehicle) in a manner that required seminal proteins. Semen amyloids did not promote decidualization and induced weak transcriptomic and secretomic responses in eSFs. In contrast, fractionated SP enriched for seminal microvesicles (MVs) promoted decidualization. IL-11 was one of the most potently SP-induced genes in eSFs and was important for SP-facilitated decidualization.Large scale dataRNAseq data were deposited in the Gene Expression Omnibus repository under series accession number GSE135640.Limitations, reasons for cautionThis study is limited to in vitro analyses.Wider implications of the findingsOur results support the notion that SP promotes decidualization, including within eSFs from women with inflammatory disorders. Despite the general ability of amyloids to induce cytokines known to be important for implantation, semen amyloids poorly signaled to eSFs and did not promote their decidualization. In contrast, fractionated SP enriched for MVs promoted decidualization and induced a transcriptional response in eSFs that overlapped with that of SP. Our results suggest that SP constituents, possibly those associated with MVs, can promote decidualization of eSFs in an IL-11-dependent manner in preparation for implantation.Study funding/competing interest(s)This project was supported by NIH (R21AI116252, R21AI122821 and R01AI127219) to N.R.R. and (P50HD055764) to L.C.G. The authors declare no conflict of interest

Evaluating a New Class of AKT/mTOR Activators for HIV Latency Reversing Activity Ex Vivo and In Vivo.

An ability to activate latent HIV-1 expression could benefit many HIV cure strategies, but the first generation of latency reversing agents (LRAs) has proven disappointing. We evaluated AKT/mTOR activators as a potential new class of LRAs. Two glycogen synthase kinase-3 inhibitors (GSK-3i's), SB-216763 and tideglusib (the latter already in phase II clinical trials) that activate AKT/mTOR signaling were tested. These GSK-3i's reactivated latent HIV-1 present in blood samples from aviremic individuals on antiretroviral therapy (ART) in the absence of T cell activation, release of inflammatory cytokines, cell toxicity, or impaired effector function of cytotoxic T lymphocytes or NK cells. However, when administered in vivo to SIV-infected rhesus macaques on suppressive ART, tideglusib exhibited poor pharmacodynamic properties and resulted in no clear evidence of significant SIV latency reversal. Whether alternative pharmacological formulations or combinations of this drug with other classes of LRAs will lead to an effective in vivo latency-reversing strategy remains to be determined.IMPORTANCE If combined with immune therapeutics, latency reversing agents (LRAs) have the potential to reduce the size of the reservoir sufficiently that an engineered immune response can control the virus in the absence of antiretroviral therapy. We have identified a new class of LRAs that do not induce T-cell activation and that are able to potentiate, rather than inhibit, CD8+ T and NK cell cytotoxic effector functions. This new class of LRAs corresponds to inhibitors of glycogen synthase kinase-3. In this work, we have also studied the effects of one member of this drug class, tideglusib, in SIV-infected rhesus monkeys. When tested in vivo, however, tideglusib showed unfavorable pharmacokinetic properties, which resulted in lack of SIV latency reversal. The disconnect between our ex vivo and in vivo results highlights the importance of developing next generation LRAs with pharmacological properties that allow systemic drug delivery in relevant anatomical compartments harboring latent reservoirs

Averting biodiversity collapse in tropical forest protected areas

The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon. With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses. As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world’s major tropical regions. Our analysis reveals great variation in reserve ‘health’: about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.William F. Laurance, D. Carolina Useche, Julio Rendeiro, Margareta Kalka, Corey J. A. Bradshaw, Sean P. Sloan, Susan G. Laurance, Mason Campbell, Kate Abernethy, Patricia Alvarez, Victor Arroyo-Rodriguez, Peter Ashton, Julieta Benítez-Malvido, Allard Blom, Kadiri S. Bobo, Charles H. Cannon, Min Cao, Richard Carroll, Colin Chapman, Rosamond Coates, Marina Cords, Finn Danielsen, Bart De Dijn, Eric Dinerstein, Maureen A. Donnelly, David Edwards, Felicity Edwards, Nina Farwig, Peter Fashing, Pierre-Michel Forget, Mercedes Foster, George Gale, David Harris, Rhett Harrison, John Hart, Sarah Karpanty, W. John Kress, Jagdish Krishnaswamy, Willis Logsdon, Jon Lovett, William Magnusson, Fiona Maisels, Andrew R. Marshall, Deedra McClearn, Divya Mudappa, Martin R. Nielsen, Richard Pearson, Nigel Pitman, Jan van der Ploeg, Andrew Plumptre, John Poulsen, Mauricio Quesada, Hugo Rainey, Douglas Robinson, Christiane Roetgers, Francesco Rovero, Frederick Scatena, Christian Schulze, Douglas Sheil, Thomas Struhsaker, John Terborgh, Duncan Thomas, Robert Timm, J. Nicolas Urbina-Cardona, Karthikeyan Vasudevan, S. Joseph Wright, Juan Carlos Arias-G., Luzmila Arroyo, Mark Ashton, Philippe Auzel, Dennis Babaasa, Fred Babweteera, Patrick Baker, Olaf Banki, Margot Bass, Inogwabini Bila-Isia, Stephen Blake, Warren Brockelman, Nicholas Brokaw, Carsten A. Brühl, Sarayudh Bunyavejchewin, Jung-Tai Chao, Jerome Chave, Ravi Chellam, Connie J. Clark, José Clavijo, Robert Congdon, Richard Corlett, H. S. Dattaraja, Chittaranjan Dave, Glyn Davies, Beatriz de Mello Beisiegel, Rosa de Nazaré Paes da Silva, Anthony Di Fiore, Arvin Diesmos, Rodolfo Dirzo, Diane Doran-Sheehy, Mitchell Eaton, Louise Emmons, Alejandro Estrada, Corneille Ewango, Linda Fedigan, François Feer, Barbara Fruth, Jacalyn Giacalone Willis, Uromi Goodale, Steven Goodman, Juan C. Guix, Paul Guthiga, William Haber, Keith Hamer, Ilka Herbinger, Jane Hill, Zhongliang Huang, I Fang Sun, Kalan Ickes, Akira Itoh, Natália Ivanauskas, Betsy Jackes, John Janovec, Daniel Janzen, Mo Jiangming, Chen Jin, Trevor Jones, Hermes Justiniano, Elisabeth Kalko, Aventino Kasangaki, Timothy Killeen, Hen-biau King, Erik Klop, Cheryl Knott, Inza Koné, Enoka Kudavidanage, José Lahoz da Silva Ribeiro, John Lattke, Richard Laval, Robert Lawton, Miguel Leal, Mark Leighton, Miguel Lentino, Cristiane Leonel, Jeremy Lindsell, Lee Ling-Ling, K. Eduard Linsenmair, Elizabeth Losos, Ariel Lugo, Jeremiah Lwanga, Andrew L. Mack, Marlucia Martins, W. Scott McGraw, Roan McNab, Luciano Montag, Jo Myers Thompson, Jacob Nabe-Nielsen, Michiko Nakagawa, Sanjay Nepal, Marilyn Norconk, Vojtech Novotny, Sean O'Donnell, Muse Opiang, Paul Ouboter, Kenneth Parker, N. Parthasarathy, Kátia Pisciotta, Dewi Prawiradilaga, Catherine Pringle, Subaraj Rajathurai, Ulrich Reichard, Gay Reinartz, Katherine Renton, Glen Reynolds, Vernon Reynolds, Erin Riley, Mark-Oliver Rödel, Jessica Rothman, Philip Round, Shoko Sakai, Tania Sanaiotti, Tommaso Savini, Gertrud Schaab, John Seidensticker, Alhaji Siaka, Miles R. Silman, Thomas B. Smith, Samuel Soares de Almeida, Navjot Sodhi, Craig Stanford, Kristine Stewart, Emma Stokes, Kathryn E. Stoner, Raman Sukumar, Martin Surbeck, Mathias Tobler, Teja Tscharntke, Andrea Turkalo, Govindaswamy Umapathy, Merlijn van Weerd, Jorge Vega Rivera, Meena Venkataraman, Linda Venn, Carlos Verea, Carolina Volkmer de Castilho, Matthias Waltert, Benjamin Wang, David Watts, William Weber, Paige West, David Whitacre, Ken Whitney, David Wilkie, Stephen Williams, Debra D. Wright, Patricia Wright, Lu Xiankai, Pralad Yonzon & Franky Zamzan