Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Multidimensional signals and analytic flexibility: Estimating degrees of freedom in human speech analyses

Recent empirical studies have highlighted the large degree of analytic flexibility in data analysis which can lead to substantially different conclusions based on the same data set. Thus, researchers have expressed their concerns that these researcher degrees of freedom might facilitate bias and can lead to claims that do not stand the test of time. Even greater flexibility is to be expected in fields in which the primary data lend themselves to a variety of possible operationalizations. The multidimensional, temporally extended nature of speech constitutes an ideal testing ground for assessing the variability in analytic approaches, which derives not only from aspects of statistical modeling, but also from decisions regarding the quantification of the measured behavior. In the present study, we gave the same speech production data set to 46 teams of researchers and asked them to answer the same research question, resulting insubstantial variability in reported effect sizes and their interpretation. Using Bayesian meta-analytic tools, we further find little to no evidence that the observed variability can be explained by analysts’ prior beliefs, expertise or the perceived quality of their analyses. In light of this idiosyncratic variability, we recommend that researchers more transparently share details of their analysis, strengthen the link between theoretical construct and quantitative system and calibrate their (un)certainty in their conclusions

Five Fishes, Five Faces: Comparative Functional Morphology of the Feeding Apparatus in Sculpins (Cottoidea)

By studying variation in feeding apparatus morphology across similar sympatric species, we can better understand the evolutionary relationships and ecological niches of these species. The most common feeding technique among vertebrates is suction feeding, in which an animal rapidly expands its buccal cavity to create negative pressure and suck in prey. Suction feeders not only open their jaws quickly; they must also close them rapidly to prevent elusive prey from escaping. In this study, we compared jaw morphology and feeding kinematics of five species of Salish Sea sculpin. We used anatomical dissection to measure differences in jaw adductor morphology and jaw leverage, and we used Sonometric crystal implantation to measure gape change and muscle strain during feeding. Although we found high conservation of body length to muscle mass ratio among species, visual inspection of the head and jaw revealed important differences. We found that the red Irish lord (Hemilepidotus hemilepidotus) possessed the fastest jaw, as demonstrated by anatomical measurement of a small lever ratio, kinematic measurement of a large gape-change to muscle-strain ratio, and behavioral observation of the red Irish lord’s ambush hunting strategy. This study highlights the importance of including behavior and ecology in analyses of organismal morphology

Five Fishes, Five Faces: Comparative Functional Morphology of the Feeding Apparatus in Sculpins (Cottoidea)

By studying variation in feeding apparatus morphology across similar sympatric species, we can better understand the evolutionary relationships and ecological niches of these species. The most common feeding technique among vertebrates is suction feeding, in which an animal rapidly expands its buccal cavity to create negative pressure and suck in prey. Suction feeders not only open their jaws quickly; they must also close them rapidly to prevent elusive prey from escaping. In this study, we compared jaw morphology and feeding kinematics of five species of Salish Sea sculpin. We used anatomical dissection to measure differences in jaw adductor morphology and jaw leverage, and we used Sonometric crystal implantation to measure gape change and muscle strain during feeding. Although we found high conservation of body length to muscle mass ratio among species, visual inspection of the head and jaw revealed important differences. We found that the red Irish lord (Hemilepidotus hemilepidotus) possessed the fastest jaw, as demonstrated by anatomical measurement of a small lever ratio, kinematic measurement of a large gape-change to muscle-strain ratio, and behavioral observation of the red Irish lord’s ambush hunting strategy. This study highlights the importance of including behavior and ecology in analyses of organismal morphology

Bigger, Stronger but Not Faster: ontogenetic change in the jaw biomechanics of the great sculpin, Myoxocephalus polyacanthocephalus

Suction feeding is the most common vertebrate feeding mode. Fishes suction feed by rapidly expanding the buccal cavity, creating a subambient pressure inside the mouth that causes water (and, ideally, a prey item) to rush in. The predator’s ability to close the mouth around evasive prey determines feeding success. As a fish grows, the volume it engulfs should scale with length to the third power (volume ∝ length3). This becomes a burden on larger fishes, as muscle force (which drives mouth closing) should scale with length squared (force ∝ muscle cross-sectional area ∝ length2). Since suction volume increases faster with size than muscle force, a force deficit results as fish grow larger. Two ways to counteract this deficit are to increase muscle mass or increase skeletal leverage within the jaw. In this study, we examined musculoskeletal variation in anatomy and kinematics across an ontogenetic series in the suction-feeding great sculpin, Myoxocephalus polyacanthocephalus. Our results show that great sculpin mandibles change shape as they grow, increasing jaw-closing muscle leverage, which counters the force deficit (N = 6, p = 0.0456). Kinematic results agree: a given amount of muscle strain produces less jaw displacement in larger fish (N = 6, p > 0.00015). We did not find disproportionate changes in muscle mass with size (N = 7, p=.514). Smaller fish, therefore, rely on high-velocity jaw closing whereas larger fish rely more on high forces to close the jaw. We hypothesize that a smaller fish needs high speed to reduce the risk of prey escape from a small suction volume, whereas a large fish needs high forces to move the disproportionately large volume of water

Bigger, Stronger but Not Faster: ontogenetic change in the jaw biomechanics of the great sculpin, Myoxocephalus polyacanthocephalus

Suction feeding is the most common vertebrate feeding mode. Fishes suction feed by rapidly expanding the buccal cavity, creating a subambient pressure inside the mouth that causes water (and, ideally, a prey item) to rush in. The predator’s ability to close the mouth around evasive prey determines feeding success. As a fish grows, the volume it engulfs should scale with length to the third power (volume ∝ length3). This becomes a burden on larger fishes, as muscle force (which drives mouth closing) should scale with length squared (force ∝ muscle cross-sectional area ∝ length2). Since suction volume increases faster with size than muscle force, a force deficit results as fish grow larger. Two ways to counteract this deficit are to increase muscle mass or increase skeletal leverage within the jaw. In this study, we examined musculoskeletal variation in anatomy and kinematics across an ontogenetic series in the suction-feeding great sculpin, Myoxocephalus polyacanthocephalus. Our results show that great sculpin mandibles change shape as they grow, increasing jaw-closing muscle leverage, which counters the force deficit (N = 6, p = 0.0456). Kinematic results agree: a given amount of muscle strain produces less jaw displacement in larger fish (N = 6, p > 0.00015). We did not find disproportionate changes in muscle mass with size (N = 7, p=.514). Smaller fish, therefore, rely on high-velocity jaw closing whereas larger fish rely more on high forces to close the jaw. We hypothesize that a smaller fish needs high speed to reduce the risk of prey escape from a small suction volume, whereas a large fish needs high forces to move the disproportionately large volume of water

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes.

Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes

Research in autophagy continues to accelerate, and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose. There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.