Evidence for the earliest structural use of wood at least 476,000 years ago.

Wood artefacts rarely survive from the Early Stone Age since they require exceptional conditions for preservation; consequently, we have limited information about when and how hominins used this basic raw material1. We report here on the earliest evidence for structural use of wood in the archaeological record. Waterlogged deposits at the archaeological site of Kalambo Falls, Zambia, dated by luminescence to at least 476 ± 23 kyr ago (ka), preserved two interlocking logs joined transversely by an intentionally cut notch. This construction has no known parallels in the African or Eurasian Palaeolithic. The earliest known wood artefact is a fragment of polished plank from the Acheulean site of Gesher Benot Ya'aqov, Israel, more than 780 ka (refs. 2,3). Wooden tools for foraging and hunting appear 400 ka in Europe4-8, China9 and possibly Africa10. At Kalambo we also recovered four wood tools from 390 ka to 324 ka, including a wedge, digging stick, cut log and notched branch. The finds show an unexpected early diversity of forms and the capacity to shape tree trunks into large combined structures. These new data not only extend the age range of woodworking in Africa but expand our understanding of the technical cognition of early hominins11, forcing re-examination of the use of trees in the history of technology12,13.

Estimation of sleep disturbances using wrist actigraphy in patients with postural tachycardia syndrome.

STUDY OBJECTIVES: Patients with postural tachycardia syndrome (POTS) commonly complain of fatigue, unrefreshing sleep, daytime sleepiness and diminished quality of life. The study objective was to assess sleep quality in POTS patients using wrist actigraphy. DESIGN: Prospective study with control group. METHODS: Patients with POTS (n = 36) and healthy subjects (n = 36) completed a detailed sleep log and actigraphy for 7 days. RESULTS: Compared with healthy subjects, POTS patients have more self-reported problems including days with restless sleep (53 ± 30% vs. 21 ± 20%; P<0.001) and tiredness (75 ± 23% vs. 39 ± 27%; P<0.001). Using actigraphy, POTS patients have lower sleep efficiency (73 ± 13% vs. 79 ± 6%; P = 0.01). Actigraphy determined sleep onset latency (SOL) did not vary significantly in the two groups, but subjective SOL was higher in POTS patient (56 ± 66 min vs. 1 3 ± 9 min; P = 0.001). In POTS patients, there was a significant correlation between subjective complaints of tiredness and actigraphic sleep efficiency (Rs = -0.36; R(2) = 0.15; P = 0.01), significant correlations between actigraphic SOL and upright norepinephrine levels (P = 0.040), and between wake after sleep onset and standing heart rate (P = 0.02). CONCLUSIONS: POTS patients have more sleep-related symptoms and poor sleep efficiency. The pattern of subjective vs. objective SOL mismatch is suggestive of sleep-state misperception. High norepinephrine correlated with actigraphic SOL, and this activation of the stress system may contribute significantly to a hyperarousal state with consequent insomnia, poor mental and physical health in POTS patients.

C. elegans telomeres contain G-strand and C-strand overhangs that are bound by distinct proteins.

Single-strand extensions of the G strand of telomeres are known to be critical for chromosome-end protection and length regulation. Here, we report that in C. elegans, chromosome termini possess 3' G-strand overhangs as well as 5' C-strand overhangs. C tails are as abundant as G tails and are generated by a well-regulated process. These two classes of overhangs are bound by two single-stranded DNA binding proteins, CeOB1 and CeOB2, which exhibit specificity for G-rich or C-rich telomeric DNA. Strains of worms deleted for CeOB1 have elongated telomeres as well as extended G tails, whereas CeOB2 deficiency leads to telomere-length heterogeneity. Both CeOB1 and CeOB2 contain OB (oligo-saccharide/oligo-nucleotide binding) folds, which exhibit structural similarity to the second and first OB folds of the mammalian telomere binding protein hPOT1, respectively. Our results suggest that C. elegans telomere homeostasis relies on a novel mechanism that involves 5' and 3' single-stranded termini.

Defective telomere lagging strand synthesis in cells lacking WRN helicase activity.

Cells from Werner syndrome patients are characterized by slow growth rates, premature senescence, accelerated telomere shortening rates, and genome instability. The syndrome is caused by the loss of the RecQ helicase WRN, but the underlying molecular mechanism is unclear. Here we report that cells lacking WRN exhibit deletion of telomeres from single sister chromatids. Only telomeres replicated by lagging strand synthesis were affected, and prevention of loss of individual telomeres was dependent on the helicase activity of WRN. Telomere loss could be counteracted by telomerase activity. We propose that WRN is necessary for efficient replication of G-rich telomeric DNA, preventing telomere dysfunction and consequent genomic instability.