67 research outputs found
The A component (SmhA) of a tripartite pore-forming toxin from Serratia marcescens: expression, purification and crystallographic analysis
Tripartite α-pore-forming toxins are constructed of three proteins (A, B and C) and are found in many bacterial pathogens. While structures of the B and C components from Gram-negative bacteria have been described, the structure of the A component of a Gram-negative α-pore-forming toxin has so far proved elusive. SmhA, the A component from the opportunistic human pathogen Serratia marcescens, has been cloned, overexpressed and purified. Crystals were grown of selenomethionine-derivatized protein and anomalous data were collected. Phases were calculated and an initial electron-density map was produced
Osteogenic tumour in Australopithecus sediba: Earliest hominin evidence for neoplastic disease
We describe the earliest evidence for neoplastic disease in the hominin lineage. This is reported
from the type specimen of the extinct hominin Australopithecus sediba from Malapa, South Africa,
dated to 1.98 million years ago. The affected individual was male and developmentally equivalent
to a human child of 12 to 13 years of age. A penetrating lytic lesion affected the sixth thoracic
vertebra. The lesion was macroscopically evaluated and internally imaged through phase-contrast
X-ray synchrotron microtomography. A comprehensive differential diagnosis was undertaken
based on gross- and micro-morphology of the lesion, leading to a probable diagnosis of osteoid
osteoma. These neoplasms are solitary, benign, osteoid and bone-forming tumours, formed from
well-vascularised connective tissue within which there is active production of osteoid and woven
bone. Tumours of any kind are rare in archaeological populations, and are all but unknown in
the hominin record, highlighting the importance of this discovery. The presence of this disease
at Malapa predates the earliest evidence of malignant neoplasia in the hominin fossil record by
perhaps 200 000 years.NCS201
Periodic Orbits and Escapes in Dynamical Systems
We study the periodic orbits and the escapes in two different dynamical
systems, namely (1) a classical system of two coupled oscillators, and (2) the
Manko-Novikov metric (1992) which is a perturbation of the Kerr metric (a
general relativistic system). We find their simple periodic orbits, their
characteristics and their stability. Then we find their ordered and chaotic
domains. As the energy goes beyond the escape energy, most chaotic orbits
escape. In the first case we consider escapes to infinity, while in the second
case we emphasize escapes to the central "bumpy" black hole. When the energy
reaches its escape value a particular family of periodic orbits reaches an
infinite period and then the family disappears (the orbit escapes). As this
family approaches termination it undergoes an infinity of equal period and
double period bifurcations at transitions from stability to instability and
vice versa. The bifurcating families continue to exist beyond the escape
energy. We study the forms of the phase space for various energies, and the
statistics of the chaotic and escaping orbits. The proportion of these orbits
increases abruptly as the energy goes beyond the escape energy.Comment: 28 pages, 23 figures, accepted in "Celestial Mechanics and Dynamical
Astronomy
New fossil remains of Homo naledi from the Lesedi Chamber, South Africa
The Rising Star cave system has produced abundant fossil hominin remains within the
Dinaledi Chamber, representing a minimum of 15 individuals attributed to Homo naledi. Further
exploration led to the discovery of hominin material, now comprising 131 hominin specimens,
within a second chamber, the Lesedi Chamber. The Lesedi Chamber is far separated from the
Dinaledi Chamber within the Rising Star cave system, and represents a second depositional context
for hominin remains. In each of three collection areas within the Lesedi Chamber, diagnostic
skeletal material allows a clear attribution to H. naledi. Both adult and immature material is present.
The hominin remains represent at least three individuals based upon duplication of elements, but
more individuals are likely present based upon the spatial context. The most significant specimen is
the near-complete cranium of a large individual, designated LES1, with an endocranial volume of
approximately 610 ml and associated postcranial remains. The Lesedi Chamber skeletal sample
extends our knowledge of the morphology and variation of H. naledi, and evidence of H. naledi
from both recovery localities shows a consistent pattern of differentiation from other hominin
species.SP201
Homo naledi, a new species of the genus Homo from the Dinaledi Chamber, South Africa.
Homo naledi is a previously-unknown species of extinct hominin discovered within the Dinaledi Chamber of the Rising Star cave system, Cradle of Humankind, South Africa. This species is characterized by body mass and stature similar to small-bodied human populations but a small endocranial volume similar to australopiths. Cranial morphology of H. naledi is unique, but most similar to early Homo species including Homo erectus, Homo habilis or Homo rudolfensis. While primitive, the dentition is generally small and simple in occlusal morphology. H. naledi has humanlike manipulatory adaptations of the hand and wrist. It also exhibits a humanlike foot and lower limb. These humanlike aspects are contrasted in the postcrania with a more primitive or australopith-like trunk, shoulder, pelvis and proximal femur. Representing at least 15 individuals with most skeletal elements repeated multiple times, this is the largest assemblage of a single species of hominins yet discovered in Africa
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Track A Basic Science
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd
Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial
Background:
Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19.
Methods:
This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.
Findings:
Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79).
Interpretation:
In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes.
Funding:
UK Research and Innovation (Medical Research Council) and National Institute of Health Research
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