Enteroendocrine cells populate gastrointestinal tissues and are known to translate local cues into systemic responses through the release of hormones into the bloodstream.
Here we report a novel ...function of enteroendocrine cells acting as local regulators of intestinal stem cell (ISC) proliferation through modulation of the mesenchymal stem cell niche in the Drosophila midgut. This paracrine signaling acts to constrain ISC proliferation within the epithelial compartment. Mechanistically, midgut enteroendocrine cells secrete the neuroendocrine hormone Bursicon, which acts—beyond its known roles in development—as a paracrine factor on the visceral muscle (VM). Bursicon binding to its receptor, DLGR2, the ortholog of mammalian leucine-rich repeat-containing G protein-coupled receptors (LGR4-6), represses the production of the VM-derived EGF-like growth factor Vein through activation of cAMP.
We therefore identify a novel paradigm in the regulation of ISC quiescence involving the conserved ligand/receptor Bursicon/DLGR2 and a previously unrecognized tissue-intrinsic role of enteroendocrine cells.
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•Enteroendocrine cells control the local stem cell niche via Bursicon•Enteroendocrine cells express the Bursicon ligand, and the muscle its receptor, DLGR2•Bursicon/DLGR2 signaling increases cAMP in visceral muscle to control EGF-like Vein•Bursicon signaling in the adult midgut instructs intestinal stem cell quiescence
Scopelliti et al. show that in the adult Drosophila midgut, enteroendocrine cells act locally—using Bursicon/DLGR2 signaling—to restrain stem cell proliferation via paracrine signaling to the mesenchymal stem cell niche.
The protease thrombin is required for normal hemostasis and pathologic thrombogenesis. Since the mechanism of coagulation factor XI (FXI)–dependent thrombus growth remains unclear, we investigated ...the contribution of FXI to thrombus formation in a primate thrombosis model. Pretreatment of baboons with a novel anti–human FXI monoclonal antibody (aXIMab; 2 mg/kg) inhibited plasma FXI by at least 99% for 10 days, and suppressed thrombin-antithrombin (TAT) complex and β-thromboglobulin (βTG) formation measured immediately downstream from thrombi forming within collagen-coated vascular grafts. FXI inhibition with aXIMab limited platelet and fibrin deposition in 4-mm diameter grafts without an apparent increase in D-dimer release from thrombi, and prevented the occlusion of 2-mm diameter grafts without affecting template bleeding times. In comparison, pretreatment with aspirin (32 mg/kg) prolonged bleeding times but failed to prevent graft occlusion, supporting the concept that FXI blockade may offer therapeutic advantages over other antithrombotic agents in terms of bleeding complications. In whole blood, aXIMab prevented fibrin formation in a collagen-coated flow chamber, independent of factor XII and factor VII. These data suggest that endogenous FXI contributes to arterial thrombus propagation through a striking amplification of thrombin generation at the thrombus luminal surface.
Hominid fossils predating the emergence of Australopithecus have been sparse and fragmentary. The evolution of our lineage after the last common ancestor we shared with chimpanzees has therefore ...remained unclear. Ardipithecus ramidus, recovered in ecologically and temporally resolved contexts in Ethiopia's Afar Rift, now illuminates earlier hominid paleobiology and aspects of extant African ape evolution. More than 110 specimens recovered from 4.4-million-year-old sediments include a partial skeleton with much of the skull, hands, feet, limbs, and pelvis. This hominid combined arboreal palmigrade clambering and careful climbing with a form of terrestrial bipedality more primitive than that of AUSTRALOPITHECUS: Ar. ramidus had a reduced canine/premolar complex and a little-derived cranial morphology and consumed a predominantly C₃ plant-based diet (plants using the C₃ photosynthetic pathway). Its ecological habitat appears to have been largely woodland-focused. Ar. ramidus lacks any characters typical of suspension, vertical climbing, or knuckle-walking. Ar. ramidus indicates that despite the genetic similarities of living humans and chimpanzees, the ancestor we last shared probably differed substantially from any extant African ape. Hominids and extant African apes have each become highly specialized through very different evolutionary pathways. This evidence also illuminates the origins of orthogrady, bipedality, ecology, diet, and social behavior in earliest Hominidae and helps to define the basal hominid adaptation, thereby accentuating the derived nature of AUSTRALOPITHECUS:
The Middle Awash Ardipithecus ramidus sample comprises over 145 teeth, including associated maxillary and mandibular sets. These help reveal the earliest stages of human evolution. Ar. ramidus lacks ...the postcanine megadontia of AUSTRALOPITHECUS: Its molars have thinner enamel and are functionally less durable than those of Australopithecus but lack the derived Pan pattern of thin occlusal enamel associated with ripe-fruit frugivory. The Ar. ramidus dental morphology and wear pattern are consistent with a partially terrestrial, omnivorous/frugivorous niche. Analyses show that the ARA-VP-6/500 skeleton is female and that Ar. ramidus was nearly monomorphic in canine size and shape. The canine/lower third premolar complex indicates a reduction of canine size and honing capacity early in hominid evolution, possibly driven by selection targeted on the male upper canine.
The Ardipithecus ramidus hand and wrist exhibit none of the derived mechanisms that restrict motion in extant great apes and are reminiscent of those of Miocene apes, such as PROCONSUL: The capitate ...head is more palmar than in all other known hominoids, permitting extreme midcarpal dorsiflexion. Ar. ramidus and all later hominids lack the carpometacarpal articular and ligamentous specializations of extant apes. Manual proportions are unlike those of any extant ape. Metacarpals 2 through 5 are relatively short, lacking any morphological traits associable with knuckle-walking. Humeral and ulnar characters are primitive and like those of later hominids. The Ar. ramidus forelimb complex implies palmigrady during bridging and careful climbing and exhibits none of the adaptations to vertical climbing, forelimb suspension, and knuckle-walking that are seen in extant African apes.
Several elements of the Ardipithecus ramidus foot are preserved, primarily in the ARA-VP-6/500 partial skeleton. The foot has a widely abducent hallux, which was not propulsive during terrestrial ...bipedality. However, it lacks the highly derived tarsometatarsal laxity and inversion in extant African apes that provide maximum conformity to substrates during vertical climbing. Instead, it exhibits primitive characters that maintain plantar rigidity from foot-flat through toe-off, reminiscent of some Miocene apes and Old World monkeys. Moreover, the action of the fibularis longus muscle was more like its homolog in Old World monkeys than in African apes. Phalangeal lengths were most similar to those of GORILLA: The Ardipithecus gait pattern would thus have been unique among known primates. The last common ancestor of hominids and chimpanzees was therefore a careful climber that retained adaptations to above-branch plantigrady.
•We evaluated FTWs for use in treating runoff from commercial nurseries.•High and low nutrient concentrations were assessed in replicated mesocosms.•FTW plants included Pontederia cordata and Juncus ...effusus, grown in Beemat rafts.•Pontederia removed over 90% of total phosphorus and over 84% of total nitrogen.•Pontederia performed significantly better than Juncus.
Floating treatment wetlands (FTWs) are an emerging surface water treatment practice for reducing nutrients such as nitrogen (N) and phosphorus (P) in a variety of waste streams. FTWs consist of floating rafts which support wetland plants allowing the plant roots to be submerged below the water surface similar to hydroponic systems. N and P removal is achieved through direct plant uptake and flocculation or sedimentation facilitated by biofilms adhering to plant roots. While research has documented FTW performance for a variety of waste streams, little information is available on runoff from commercial nurseries. Nursery runoff occurs frequently, from storm and irrigation events, and can potentially contain elevated concentrations of total N (TN) and total P (TP) due to crop fertilization and frequent irrigation. Nursery runoff is often captured in large ponds known as tailwater recovery basins (TRBs) for reuse. We assessed the effectiveness of FTWs for treating nursery runoff in TRBs over a 7-day hydraulic retention time across a 19-week growing season using two supplied nutrient concentrations and four treatments with four replicates in a randomized complete block mesocosm experiment. The high nutrient concentration averaged 17.1 mg·L−1 TN and 2.61 mg·L−1 TP and low nutrient concentration averaged 5.22 mg·L−1 TN and 0.52 mg·L−1 TP. Treatments included: 1) Pontederia cordata, 2) Juncus effusus, 3) a raft with no plants, and 4) no raft (open-water). Pontederia cordata removed 90% and 92% of TP and 84% and 89% TN, depending on initial loading; performing better than the other planted and non-planted treatments. Juncus effusus performed better than the mat-only control treatments for TP and TN removal across nutrient concentrations tested, but performed similarly to the open water control when nutrient load was evaluated. Nutrient uptake by Pontederia cordata averaged 0.026 g·m−2·d−1 N and 0.0075 g·m−2·d−1 P. The study demonstrated that FTWs can be very effective, but nutrient removal depends greatly upon plant species selection.
Hominid fossils predating the emergence of Australopithecus have been sparse and fragmentary. The evolution of our lineage after the last common ancestor we shared with chimpanzees has therefore ...remained unclear. Ardipithecus ramidus, recovered in ecologically and temporally resolved contexts in Ethiopia's Afar Rift, now illuminates earlier hominid paleobiology and aspects of extant African ape evolution. More than 110 specimens recovered from 4.4-million-year-old sediments include a partial skeleton with much of the skull, hands, feet, limbs, and pelvis. This hominid combined arboreal palmigrade clambering and careful climbing with a form of terrestrial bipedality more primitive than that of Australopithecus. Ar. ramidus had a reduced canine/premolar complex and a little-derived cranial morphology and consumed a predominantly C₃ plant-based diet (plants using the C₃ photosynthetic pathway). Its ecological habitat appears to have been largely woodland-focused. Ar. ramidus lacks any characters typical of suspension, vertical climbing, or knuckle-walking. Ar. ramidus indicates that despite the genetic similarities of living humans and chimpanzees, the ancestor we last shared probably differed substantially from any extant African ape. Hominids and extant African apes have each become highly specialized through very different evolutionary pathways. This evidence also illuminates the origins of orthogrady, bipedality, ecology, diet, and social behavior in earliest Hominidae and helps to define the basal hominid adaptation, thereby accentuating the derived nature of Australopithecus.
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