The new Australasian goblin spider genus Prethopalpus (Araneae, Oonopidae)

The new goblin spider genus Prethopalpus is restricted to the Australasian tropics, from the lower Himalayan Mountains in Nepal and India to the Malaysian Peninsula, Indonesia, Papua New Guinea, and Australia. Prethopalpus contains those species with a swollen palpal patella, which is one to two times the size of the femur, together with a cymbium and bulb that is usually separated, although it is largely fused in four species. The type species Opopaea fosuma Burger et al. from Sumatra, and Camptoscaphiella infernalis Harvey and Edward from Western Australia are newly transferred to Prethopalpus. The genus consists of 41 species of which 39 are newly described: P. ilam Baehr (♂, ♀) from Nepal; P. khasi Baehr (♂), P. madurai Baehr (♂), P. mahanadi Baehr (♂, ♀), and P. meghalaya Baehr (♂, ♀) from India; P. bali Baehr (♂), P. bellicosus Baehr and Thoma (♂, ♀), P. brunei Baehr (♂, ♀), P. deelemanae Baehr and Thoma (♂), P. java Baehr (♂, ♀), P. kranzae Baehr (♂), P. kropfi Baehr (♂, ♀), P. leuser Baehr (♂, ♀), P. magnocularis Baehr and Thoma (♂), P. pahang Baehr (♂), P. perak Baehr (♂, ♀), P. sabah Baehr (♂, ♀), P. sarawak Baehr (♂), P. schwendingeri Baehr (♂, ♀), and P. utara Baehr (♂, ♀) from Indonesia and Malaysia; and P. alexanderi Baehr and Harvey (♂), P. attenboroughi Baehr and Harvey (♂), P. blosfeldsorum Baehr and Harvey (♂), P. boltoni Baehr and Harvey (♂, ♀), P. callani Baehr and Harvey (♂, ♀), P. cooperi Baehr and Harvey (♂), P. eberhardi Baehr and Harvey (♂, ♀), P. framenaui Baehr and Harvey (♂, ♀), P. humphreysi Baehr and Harvey (♂, ♀), P. kintyre Baehr and Harvey (♂), P. scanloni Baehr and Harvey (♂), P. pearsoni Baehr and Harvey (♂), P. julianneae Baehr and Harvey (♂), P. maini Baehr and Harvey (♂, ♀), P. marionae Baehr and Harvey (♂, ♀), P. platnicki Baehr and Harvey (♂, ♀), P. oneillae Baehr and Harvey (♂), P. rawlinsoni Baehr and Harvey (♂), and P. tropicus Baehr and Harvey (♂, ♀) from Australia and Papua New Guinea. Three separate keys to species from different geographical regions are provided. Most species are recorded from single locations and only three species are more widely distributed. A significant radiation of blind troglobites comprising 14 species living in subterranean ecosystems in Western Australia is discussed. These include several species that lack abdominal scuta, a feature previously used to define subfamilies of Oonopidae.

Jackson County Heifer Development Project Summary

The heifer development project was a five year project conducted on the site of the former Jackson County Farm north of Andrew, Iowa, for four years and on an area producer’s farm for the fifth year. Heifers arrived around December 1 each year and the average number of heifers each year was 43 with a low of 37 and high of 47. After a 30+ day warm-up period the heifers were put on a 112-day test from early January to late April. They were fed a shelled corn and legume-grass hay ration consisting of between 13% and 14% crude protein and a range of .44 to .58 megacal/pound of NEg over the five years. During the 112-day test heifers gained 1.86, 1.78, 1.5, 1.63 and 2.2 pounds per day, respectively, for years 1992 through 1996. The actual average breeding weight was less than the target weight in three years by 5, 12 and 22 pounds and exceeded the target weight in two year by 17 and 28 pounds. Estrus synchronization used a combination of MGA feeding and Lutalyse injection. Heifers were heat detected and bred 12 hours later for a three-day period. On the fourth day, all heifers not bred were mass inseminated. Heifers then ran with the cleanup bull for 58 days. The average synchronization response rate during the project was 79%. The overall pregnancy rates based on September pregnancy averaged 92%. The five year average total cost per head for heifer development was $286.18 or about $.85 per day. Feed and pasture costs averaged 61% of the total costs.

Intensive Rotational Grazing of Steers at the Andrew Jackson Demonstration Farm

Fifty head of crossbred steers started grazing 51 acres of pasture on May 1 in a rotational grazing system using a variable density paddock system. Twenty-two head grazed 92 days, 27 grazed 140 days, and one steer died. A total of 11,922 pounds was produced on 5,804 animal-days of grazing. The average daily gain was 2.02 pounds for group 1 and 2.07 for group 2. The stocking rate for the first 92 days was .98 steers per acre and .53 for the final 48 days. The animal days of grazing per acre was 113 and the pounds of gain per acre was 233. Total return for land, labor and management for the demonstration was $2,829.76 or $55.49/acre.

Management Intensive Grazing of Stockers at the Andrew Jackson Demonstration Farm (1996 – 1998)

The Andrew Jackson Demonstration Farm (AJDF) is located in central Jackson County in east central Iowa. A board of directors operates the farm for the purpose of demonstrating different production practices and management strategies. From 1996 to 1998 management intensive grazing practices and the grazing of stockers on a combination of permanent and tillable pasture have been demonstrated. Grazing strategies or practices demonstrated during these years included establishment of Eastern Gamagrass and Big Bluestem, variable density grazing, measuring forage on-offer, estimating dry matter intake, grazing corn, pasture renovation, and fencing and water systems. Production performance data were gathered for the three years stockers that were grazed. During this time the stockers averaged 121 animal days of grazing, a 1.1 head per acre stocking rate, a 1.85 pound average daily gain, and 228 pounds of gain per acre. The financial measures evaluated the value of gain on pasture and the pasture cost of the gain. The value of gain per pound was positive for 1996 and 1997 at $.58 and $.52 whereas in 1998 it was a -$.04. Pasture costs per pound of gain ranged from $.12 to $.16. Production performance is only one part of the profit picture when evaluating a stocker operation. Buysell margins are the other significant part that can greatly impact the profit potential of a summer grazing program.

Jackson County Heifer Development Project Update

The heifer development project took place the past four years on the site of the former Jackson County Farm north of Andrew, Iowa. Heifers arrived around December 1 with 38 heifers delivered for 1992, 44 for 1993, 46 for 1994, and 47 for 1995. After a 30+ day warm-up period, the heifers were put on a 112-day test from early January to late April. They were fed a shelled corn and legume-grass hay ration consisting of between 13% and 14% crude protein and .48, .58, .44, and .54 megacal/pound of NEg respectively for the years 1992 - 1995. During the 112-day test heifers gained 1.86, 1.78, 1.5, and 1.63 pounds per day respectively for years 1992 through 1995. The 1995 heifers averaged 853 pounds at breeding (22 pounds under target weight). This compares with previous years in which the breeding weight was less than target weight in two years by 5 and 12 pounds and exceeded the target weight in one year by 17 pounds. Estrus synchronization used a combination of MGA feeding and Lutalyse injection. Heifers were heatdetected and bred 12 hours later for a three-day period. On the fourth day, all heifers not bred were mass inseminated. Heifers then ran with the cleanup bull for 58 days. The synchronization response rate in 1995 was 83%, which compares with the three year previous average of 77%. The overall pregnancy rates based on September pregnancy exams were 94.6% in 1992, 93% in 1993, 91% in 1994, and 91.5% in 1995. Development costs for the 326 days in 1995 totaled $269.14 per heifer. This compares with the average of $286. 92 for the three previous years. The four-year average total cost per head for heifer development was $282.48, or about $.84 per day. Feed and pasture costs represented 58% of the total costs, or $.49 per day.

Chronic spontaneous activity generated in the somata of primary nociceptors is associated with pain-related behavior after spinal cord injury.

Mechanisms underlying chronic pain that develops after spinal cord injury (SCI) are incompletely understood. Most research on SCI pain mechanisms has focused on neuronal alterations within pain pathways at spinal and supraspinal levels associated with inflammation and glial activation. These events might also impact central processes of primary sensory neurons, triggering in nociceptors a hyperexcitable state and spontaneous activity (SA) that drive behavioral hypersensitivity and pain. SCI can sensitize peripheral fibers of nociceptors and promote peripheral SA, but whether these effects are driven by extrinsic alterations in surrounding tissue or are intrinsic to the nociceptor, and whether similar SA occurs in nociceptors in vivo are unknown. We show that small DRG neurons from rats (Rattus norvegicus) receiving thoracic spinal injury 3 d to 8 months earlier and recorded 1 d after dissociation exhibit an elevated incidence of SA coupled with soma hyperexcitability compared with untreated and sham-treated groups. SA incidence was greatest in lumbar DRG neurons (57%) and least in cervical neurons (28%), and failed to decline over 8 months. Many sampled SA neurons were capsaicin sensitive and/or bound the nociceptive marker, isolectin B4. This intrinsic SA state was correlated with increased behavioral responsiveness to mechanical and thermal stimulation of sites below and above the injury level. Recordings from C- and Aδ-fibers revealed SCI-induced SA generated in or near the somata of the neurons in vivo. SCI promotes the entry of primary nociceptors into a chronic hyperexcitable-SA state that may provide a useful therapeutic target in some forms of persistent pain.

Enterococcus faecalis rnjB is required for pilin gene expression and biofilm formation.

Pili in Gram-positive bacteria play a major role in the colonization of host tissue and in the development of biofilms. They are promising candidates for vaccines or drug targets since they are highly immunogenic and share common structural and functional features among various Gram-positive pathogens. Numerous publications have helped build a detailed understanding of pilus surface assembly, yet regulation of pilin gene expression has not been well defined. Utilizing a monoclonal antibody developed against the Enterococcus faecalis major pilus protein EbpC, we identified mutants from a transposon (Tn) insertion library which lack surface-exposed Ebp pili. In addition to insertions in the ebp regulon, an insertion in ef1184 (dapA) significantly reduced levels of EbpC. Analysis of in-frame dapA deletion mutants and mutants with the downstream gene rnjB deleted further demonstrated that rnjB was responsible for the deficiency of EbpC. Sequence analysis revealed that rnjB encodes a putative RNase J2. Subsequent quantitative real-time PCR (qRT-PCR) and Northern blotting demonstrated that the ebpABC mRNA transcript level was significantly decreased in the rnjB deletion mutant. In addition, using a reporter gene assay, we confirmed that rnjB affects the expression of the ebpABC operon. Functionally, the rnjB deletion mutant was attenuated in its ability to produce biofilm, similar to that of an ebpABC deletion mutant which lacks Ebp pili. Together, these results demonstrate the involvement of rnjB in E. faecalis pilin gene expression and provide insight into a novel mechanism of regulation of pilus production in Gram-positive pathogens.

Long-lasting hyperexcitability induced by depolarization in the absence of detectable Ca2+ signals.

Learning and memory depend on neuronal alterations induced by electrical activity. Most examples of activity-dependent plasticity, as well as adaptive responses to neuronal injury, have been linked explicitly or implicitly to induction by Ca(2+) signals produced by depolarization. Indeed, transient Ca(2+) signals are commonly assumed to be the only effective transducers of depolarization into adaptive neuronal responses. Nevertheless, Ca(2+)-independent depolarization-induced signals might also trigger plastic changes. Establishing the existence of such signals is a challenge because procedures that eliminate Ca(2+) transients also impair neuronal viability and tolerance to cellular stress. We have taken advantage of nociceptive sensory neurons in the marine snail Aplysia, which exhibit unusual tolerance to extreme reduction of extracellular and intracellular free Ca(2+) levels. The axons of these neurons exhibit a depolarization-induced memory-like hyperexcitability that lasts a day or longer and depends on local protein synthesis for induction. Here we show that transient localized depolarization of these axons in an excised nerve-ganglion preparation or in dissociated cell culture can induce short- and intermediate-term axonal hyperexcitability as well as long-term protein synthesis-dependent hyperexcitability under conditions in which Ca(2+) entry is prevented (by bathing in nominally Ca(2+) -free solutions containing EGTA) and detectable Ca(2+) transients are eliminated (by adding BAPTA-AM). Disruption of Ca(2+) release from intracellular stores by pretreatment with thapsigargin also failed to affect induction of axonal hyperexcitability. These findings suggest that unrecognized Ca(2+)-independent signals exist that can transduce intense depolarization into adaptive cellular responses during neuronal injury, prolonged high-frequency activity, or other sustained depolarizing events.

History of Medicine Schedule and Abstracts 2009-2010

From Genes to Genome: An historical perspective (David Wheeler) Ignaz Semmelweis: Medical Prophet Without Honor (Ronald L. Young) Why Lewis Thomas, MD is Not a Bore: The Life of a Biology Watcher (Steven Greenberg) Doctors from Hell: The Horrific Account of Nazi Experiments on Humans (Vivien Spitz) Illuminating Autism: Passing the Torch from the Twentieth Century (Student Essay Contest Winners) (Lynn Yudofsky) Healing Beyond Hippocrates: The Temples of Asclepius and Public Health Care in Ancient Greece (Andrew Baldwin) Iron Wills and Iron Lungs: The Polio Years in Texas (Heather Green Wooten) William Osler and the Inspirational Uses of History (Michael Bliss) Working Too Hard and Achieving Too Much: The Cost of Being Harvey Cushing (Michael Bliss) Medicine in Ancient Egypt (Gene Boisaubin) The History of Diabetes (Jeff Unger)

Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial

BACKGROUND The addition of bevacizumab to chemotherapy improves progression-free survival in metastatic breast cancer and pathological complete response rates in the neoadjuvant setting. Micrometastases are dependent on angiogenesis, suggesting that patients might benefit from anti-angiogenic strategies in the adjuvant setting. We therefore assessed the addition of bevacizumab to chemotherapy in the adjuvant setting for women with triple-negative breast cancer. METHODS For this open-label, randomised phase 3 trial we recruited patients with centrally confirmed triple-negative operable primary invasive breast cancer from 360 sites in 37 countries. We randomly allocated patients aged 18 years or older (1:1 with block randomisation; stratified by nodal status, chemotherapy [with an anthracycline, taxane, or both], hormone receptor status [negative vs low], and type of surgery) to receive a minimum of four cycles of chemotherapy either alone or with bevacizumab (equivalent of 5 mg/kg every week for 1 year). The primary endpoint was invasive disease-free survival (IDFS). Efficacy analyses were based on the intention-to-treat population, safety analyses were done on all patients who received at least one dose of study drug, and plasma biomarker analyses were done on all treated patients consenting to biomarker analyses and providing a measurable baseline plasma sample. This trial is registered with ClinicalTrials.gov, number NCT00528567. FINDINGS Between Dec 3, 2007, and March 8, 2010, we randomly assigned 1290 patients to receive chemotherapy alone and 1301 to receive bevacizumab plus chemotherapy. Most patients received anthracycline-containing therapy; 1638 (63%) of the 2591 patients had node-negative disease. At the time of analysis of IDFS, median follow-up was 31·5 months (IQR 25·6-36·8) in the chemotherapy-alone group and 32·0 months (27·5-36·9) in the bevacizumab group. At the time of the primary analysis, IDFS events had been reported in 205 patients (16%) in the chemotherapy-alone group and in 188 patients (14%) in the bevacizumab group (hazard ratio [HR] in stratified log-rank analysis 0·87, 95% CI 0·72-1·07; p=0·18). 3-year IDFS was 82·7% (95% CI 80·5-85·0) with chemotherapy alone and 83·7% (81·4-86·0) with bevacizumab and chemotherapy. After 200 deaths, no difference in overall survival was noted between the groups (HR 0·84, 95% CI 0·64-1·12; p=0·23). Exploratory biomarker assessment suggests that patients with high pre-treatment plasma VEGFR-2 might benefit from the addition of bevacizumab (Cox interaction test p=0·029). Use of bevacizumab versus chemotherapy alone was associated with increased incidences of grade 3 or worse hypertension (154 patients [12%] vs eight patients [1%]), severe cardiac events occurring at any point during the 18-month safety reporting period (19 [1%] vs two [<0·5%]), and treatment discontinuation (bevacizumab, chemotherapy, or both; 256 [20%] vs 30 [2%]); we recorded no increase in fatal adverse events with bevacizumab (four [<0·5%] vs three [<0·5%]). INTERPRETATION Bevacizumab cannot be recommended as adjuvant treatment in unselected patients with triple-negative breast cancer. Further follow-up is needed to assess the potential effect of bevacizumab on overall survival.