Down-regulation of transforming growth factor-beta receptors: cooperativity between the types I, II, and III receptors and modulation at the cell surface.

The types I, II, and III receptors (RI, RII, RIII) for transforming growth factor-beta (TGF-beta) become down-regulated in response to ligand, presumably via their internalization from the cell surface. This report examines the down-regulation of full-length RI, RII, and RIII in cells endogenously or transiently expressing these receptors. Down-regulation occurred rapidly (within 2 h after TGF-beta1 treatment at 37 degrees C) and showed a dose response, between 10 and 200 pM TGF-beta1, in cells expressing RI, RII, and RIII (Mv1lu and A549 cells). A comparison between Mv1Lu and mutant cell derivatives R-1B (lacking RI) or DR-26 (lacking RII) indicated that all three receptors were necessary for efficient down-regulation. Down-regulation experiments, utilizing TGF-beta-treated 293 cells transiently expressing different combinations of these receptors indicated that neither RII or RIII were down-regulated when expressed alone and that RI was required for maximal down-regulation of RII. RII and RIII were partially down-regulated when these receptors were coexpressed in the absence of RI (in R-1B and 293 cells). Surprisingly, TGF-beta receptors were partially down-regulated in Mv1Lu, A549, and 293 cells treated with TGF-beta1 at 4 degrees C. Microscopic examination of 293 cells coexpressing RI fused to green fluorescent protein (RI-GFP) and RII indicated that, after treatment with TGF-beta1 at 4 degrees C, RI-GFP formed aggregates at the cell surface at this temperature. RI-GFP was not detected at the surface of these cells after TGF-beta1 treatment at 37 degrees C. Our results suggest a two phase mechanism for TGF-beta1 receptor down-regulation involving receptor modulation (aggregation) at the cell surface and internalization.     

Cutting edge: TIGIT has T cell-intrinsic inhibitory functions

Costimulatory molecules regulate the functional outcome of T cell activation, and disturbance of the balance between activating and inhibitory signals results in increased susceptibility to infection or the induction of autoimmunity. Similar to the well-characterized CD28/CTLA-4 costimulatory pathway, a newly emerging pathway consisting of CD226 and T cell Ig and ITIM domain (TIGIT) has been associated with susceptibility to multiple autoimmune diseases. In this study, we examined the role of the putative coinhibitory molecule TIGIT and show that loss of TIGIT in mice results in hyperproliferative T cell responses and increased susceptibility to autoimmunity. TIGIT is thought to indirectly inhibit T cell responses by the induction of tolerogenic dendritic cells. By generating an agonistic anti-TIGIT Ab, we demonstrate that TIGIT can inhibit T cell responses directly independent of APCs. Microarray analysis of T cells stimulated with agonistic anti-TIGIT Ab revealed that TIGIT can act directly on T cells by attenuating TCR-driven activation signals.     

Heart rate variability and short duration spaceflight: relationship to post-flight orthostatic intolerance

Background  

Upon return from space many astronauts experience symptoms of orthostatic intolerance. Research has implicated altered autonomic cardiovascular regulation due to spaceflight with further evidence to suggest that there might be pre-flight autonomic indicators of post-flight orthostatic intolerance. We used heart rate variability (HRV) to determine whether autonomic regulation of the heart in astronauts who did or did not experience post-flight orthostatic intolerance was different pre-flight and/or was differentially affected by short duration (8 – 16 days) spaceflight. HRV data from ten-minute stand tests collected from the 29 astronauts 10 days pre-flight, on landing day and three days post-flight were analysed using coarse graining spectral analysis. From the total power (P_TOT), the harmonic component was extracted and divided into high (P_HI: >0.15 Hz) and low (P_LO: = 0.15 Hz) frequency power regions. Given the distribution of autonomic nervous system activity with frequency at the sinus node, P_HI/P_TOT was used as an indicator of parasympathetic activity; P_LO/P_TOT as an indicator of sympathetic activity; and, P_LO/P_HI as an estimate of sympathovagal balance.     

Medicinal Plant Use and Health Sovereignty: Findings from the Tajik and Afghan Pamirs

Medicinal plants are indicators of indigenous knowledge in the context of political volatility and sociocultural and ecological change in the Pamir Mountains of Afghanistan and Tajikistan. Medicinal plants are the primary health care option in this region of Central Asia. The main objective of this paper is to demonstrate that medicinal plants contribute to health security and sovereignty in a time of instability. We illustrate the nutritional as well as medicinal significance of plants in the daily lives of villagers. Based on over a decade and half of research related to resilience and livelihood security, we present plant uses in the context of mountain communities. Villagers identified over 58 cultivated and noncultivated plants and described 310 distinct uses within 63 categories of treatment and prevention. Presence of knowledge about medicinal plants is directly connected to their use.     

Diversity of Plant Knowledge as an Adaptive Asset: A Case Study with Standing Rock Elders<Superscript>1</Superscript>

Diversity of Plant Knowledge as an Adaptive Asset: A Case Study with Standing Rock Elders. Indigenous knowledge is often represented as being homogeneous within cultural groups, and differences in knowledge within communities are interpreted as a lack of cultural consensus. Alternatively, differences in knowledge represent a range of possibilities for communities to respond to social and ecological change. This paper examines the diversity of plant knowledge among elders who live in the Standing Rock Nation of the northern Great Plains. Elders know how to use different plants, and also hold different knowledge about the same plants. Analysis indicates that elders each contribute unique, complementary, and seemingly contradictory plant knowledge to their community. Compiled seasonal rounds help visualize differences in knowledge about the temporal availability of plants. These differences are linked to variations in use, including references to specific gathering sites, strategies to harvest multiple species, and selection of plants at different stages of development. Elders’ diverse knowledge about the seasonal availability of plants may facilitate community adaptation to climate change in the 21st century.     

Comparative Morphometrics and Associated Growth Trends of Two Benthophagous Cichlid Species from Lake Malawi (Pisces, Perciformes)

Body shape differences between two benthophagous, sympatric cichlid species, Ctenopharynx pictus and Otopharynx sp. “heterodon nankhumba” were examined for 14 morphometric characters using measurements obtained from 11 morphological landmarks and additional 6 characters from the head region using principal component and regression analyses. The two species, though not closely related, superficially resemble each other and, being benthic feeders, directly compete for food resources unless morphological differences lead to trophic specialization. Hence, the present study explores the presence of such morphological variations. Principal component analysis (PCA), revealed that only four characters loaded highly on PC II and, therefore, account for most of the variations in the external morphology between the two species. C. pictus has longer lower jaws reflecting longer gape, and a shorter abdominal cavity than O. sp. “heterodon nakhumba”. The regression analyses showed significant differences in the allometric coefficients of the lower jaw and abdominal cavity, which might have contributed to differences in overall shape detected between the two species. The difference in gape size between the two species may be related to different feeding habits employed by each species, and such specializations are suggested to reduce interspecific competition for food resources. We suggest that the ensuing ecological separation promotes sympatry of these two species.     

Effect of saddleback syndrome and vertebral deformity on the body shape and size in hatchery-reared juvenile red spotted grouper, Epinephelus akaara (Perciformes: Serranidae): a geometric morphometric approach

This study examined how saddleback syndrome (SBS) and vertebral deformity affect the body shape and size of juvenile stage red spotted grouper, Epinephelus akaara, using the landmark‐based geometric morphometrics method. According to the criterion of skeletal conditions, three groups, i.e. vertebral deformity, SBS, and normal groups, were identified. The results revealed significant differences in body shape among the three groups, in which the vertebral‐deformed group had the deepest mid‐body, the broadest anterior part, and a shortened caudal peduncle, while the SBS group showed the shallowest mid‐body and the narrowest anterior part. The normal group had a body shape intermediate between the vertebral and SBS groups. A comparison of body size among the three groups revealed significant differences in centroid size, with the vertebral‐deformed and SBS groups showing smallest and largest centroid size, respectively. This study illuminates that not all skeletal deformities lead to smaller body size. We suggest that rearing conditions might have caused the deformities reported herein.     

Viewing Change Through the Prism of Indigenous Human Ecology: Findings from the Afghan and Tajik Pamirs

The effects of socioecological transformations such as climate change, the collapse of the Soviet empire, and civil war are examined for 14 villages in the valleys of the Pamir Mountains in the historical Badakhshan region, now divided between Afghanistan and Tajikistan. Preliminary findings indicate concern for food sovereignty, evidence of biocultural impacts of climate change, an increasing burden on women, debilitating opium addiction, the ecological importance of sacred sites, and other priorities related to sustainable livelihoods, such as energy needs (for fuel and lighting) and physical and social infrastructure in the form of roads and schools. In the complex setting of the Pamir Mountains, characterized by both cultural and ecological diversity and marked by artificial political boundaries, the creative and pragmatic interaction between indigenous and scientific knowledge sustains the best hope for survival. Applied research must combine communities of inquirers (research institutions) with communities of social practitioners (farmers, pastoralists, and civil society institutions) to facilitate indigenous participation in generating context-specific knowledge. The goal of such research is practical outcomes that will meet the urgent priorities of village communities. This paper establishes a baseline from which undertake applied human ecological research related to livelihood security.