What to do, or how to do it?

In this issue of Neuron, Ajemian et al. present a computational model of the activity of neurons in primary motor cortex (M1) during isometric movements in different postures. By modeling the output of M1 neurons in terms of their influence on muscles, they find each M1 neuron maps its output into a particular pattern of muscle actions.     

Papanicolaou stain: Is it economical to switch to rapid, economical, acetic acid, papanicolaou stain?

OBJECTIVE: To standardize an inexpensive and rapid Papanicolaou staining technique with limited ethanol usage. STUDY DESIGN: Smears from 200 patients were collected (2 per patient) and fixed in methanol. Half were subjected to conventional Papanicolaou and half to stain ing with rapid, economical, acetic acid Papanicolaou (REAP) stain. In REAP, pre-OG6 and post-OG6 and post-EA36 ethanol baths were replaced by 1% acetic acid and Scott's tap water with tap water. Hematoxylin was preheated to 60 degrees C. Final dehydration was with methanol. REAP smears were compared with Papanicolaou smears for optimal cytoplasmic and nuclear staining, stain preservation, cost and turnaround time. RESULTS: With the REAP method, cytoplasmic and nuclear staining was optimal in 181 and 192 cases, respectively. The staining time was considerably reduced, to 3 minutes, and the cost per smear was reduced to one fourth. The staining quality remained good in all the smears for > 2 years. CONCLUSION: REAP is a rapid, cost-effective alternative to Papanicolaou stain. Though low stain penetration in large cell clusters is a limitation, final interpretation was not compromised.     

VEGF: necessary to prevent motoneuron degeneration, sufficient to treat ALS?

Since Charcot recognized the devastating disorder amyotrophic lateral sclerosis (ALS) in 1874, many theories have been proposed to explain its pathogenesis, but it remains as deadly and incurable as ever. Three years ago it was reported that reduced levels of vascular endothelial growth factor (VEGF) caused ALS-like motoneuron degeneration in mice. Recent evidence indicates that insufficient VEGF is also a risk factor for ALS in humans. Although VEGF was once considered to be only a specific angiogenic factor, emerging evidence indicates that it also displays important neuroprotective activity. These insights have primed widespread interest in developing VEGF-based therapies for (moto)neuron degenerative disorders, raising new hope for the treatment of ALS and other neurodegenerative diseases.     

To spike,or when to spike?

Recent experimental reports have suggested that cortical networks can operate in regimes were sensory information is encoded by relatively small populations of spikes and their precise relative timing. Combined with the discovery of spike timing dependent plasticity, these findings have sparked growing interest in the capabilities of neurons to encode and decode spike timing based neural representations. To address these questions, a novel family of methodologically diverse supervised learning algorithms for spiking neuron models has been developed. These models have demonstrated the high capacity of simple neural architectures to operate also beyond the regime of the well established independent rate codes and to utilize theoretical advantages of spike timing as an additional coding dimension.     

Adjuvant endocrine therapy in postmenopausal hormone-sensitive breast cancer: to start, to switch or to extend?

From the big randomized clinical trials there are evidences that adjuvant endocrine therapy for hormone-sensitive early breast cancer in postmenopausal women should include an aromatase inhibitor (AI). Anastrozole or letrozole should be used upfront for 5 years (ATAC and BIG 1-98), the sequential approach of tamoxifen for 2-3 years, followed by anastrozole or exemestane for 2-3 years is a reasonable alternative (ABCSG8, ARNO 95, IES, ITA), and mostly in patients with node-positive disease completing 5 years of tamoxifen should be offered letrozole up to 4-5 years (MA-17). In each of these trials incorporation of an AI resulted in significant improvement in study endpoints. Further results will be needed to establish the optimal beneficial effect, use, duration and safety of adjuvant AI therapies.     

Aβ42 oligomers, but not fibrils, simultaneously bind to and cause damage to ganglioside-containing lipid membranes

Aβ (amyloid-β peptide) assembles to form amyloid fibres that accumulate in senile plaques associated with AD (Alzheimer's disease). The major constituent, a 42-residue Aβ, has the propensity to assemble and form soluble and potentially cytotoxic oligomers, as well as ordered stable amyloid fibres. It is widely believed that the cytotoxicity is a result of the formation of transient soluble oligomers. This observed toxicity may be associated with the ability of oligomers to associate with and cause permeation of lipid membranes. In the present study, we have investigated the ability of oligomeric and fibrillar Aβ42 to simultaneously associate with and affect the integrity of biomimetic membranes in vitro. Surface plasmon field-enhanced fluorescence spectroscopy reveals that the binding of the freshly dissolved oligomeric 42-residue peptide binds with a two-step association with the lipid bilayer, and causes disruption of the membrane resulting in leakage from vesicles. In contrast, fibrils bind with a 2-fold reduced avidity, and their addition results in approximately 2-fold less fluorophore leakage compared with oligomeric Aβ. Binding of the oligomers may be, in part, mediated by the GM1 ganglioside receptors as there is a 1.8-fold increase in oligomeric Aβ binding and a 2-fold increase in permeation compared with when GM1 is not present. Atomic force microscopy reveals the formation of defects and holes in response to oligomeric Aβ, but not preformed fibrillar Aβ. The results of the present study indicate that significant membrane disruption arises from association of low-molecular-mass Aβ and this may be mediated by mechanical damage to the membranes by Aβ aggregation. This membrane disruption may play a key role in the mechanism of Aβ-related cell toxicity in AD.     

Pannexin: to gap or not to gap, is that a question?

Vertebrates express two families of gap junction proteins: the well characterized connexins and the recently discovered pannexins. The latter are related to invertebrate innexins. Here we present the hypothesis that pannexins, rather than providing a redundant system to gap junctions formed by connexins, exert a physiological role as nonjunctional membrane channels. Specifically, we propose that pannexins can serve as ATP release channels. This function presumptively is also performed by innexins in invertebrates, in addition to their traditional gap junction role.     

Sinoalaria,a name to replace Alaria （Araneae,Theridiosomatidae）

Sinoalaria nom. nov.
= Alaria Zhao ＆ Li, 2012. ZooKeys 255： 7.
Type species. Alaria chengguanensis Zhao ＆ Li, 2012
Etymology. The generic epithet is a combination of Latin Sino （=China） and Latin alaria （=of wings）, referring to the distribution of the genus and the shape of projection of the copulatory ducts. Gender is feminine.     

HIV and HCV： from Co-infection to Epidemiology, Transmission, Pathogenesis, and Treatment

Human immunodeficiency virus (HIV) is the infectious agent causing acquired immu-nodeficiency syndrome (AIDS),a deadliest scourge of human society. Hepatitis C virus (HCV) is a major causative agent of chronic liver disease and infects an estimated 170 million people worldwide,resulting in a serious public health burden. Due to shared routes of transmission,co-infection with HIV and HCV has become common among individuals who had high risks of blood exposures. Among hemophiliacs the co-infection rate accounts for 85%; while among injection drug users (IDU) the rate can be as high as 90%. HIV can accelerate the progression of HCV-related liver disease,particularly when immunodeficiency has developed. Although the effect of HCV on HIV infection is controversial,most studies showed an increase in mortality due to liver disease. HCV may act as a direct cofactor to fasten the progression of AIDS and decrease the tolerance of highly active antiretroviral therapy (HARRT). Conversely,HAART-related hepatotoxicity may enhance the progression of liver fibrosis. Due to above complications,co-infection with HCV and HIV-1 has imposed a critical challenge in the management of these patients. In this review,we focus on the epidemiology and transmission of HIV and HCV,the impact of the two viruses on each other,and their treatment.     

Sinoinsula,a name to replace Insula （Araneae,Salticidae）

Sinoinsula nom. nov. = Insuht Zhou ＆ Li, 2013. Zootaxa 3712 （I）： 11.     

A simple,low-cost method to age mammals? An alternative to cementum annuli analysis

One of the most common and ubiquitous methods to age mammals is by counting the cementum annuli in molars, premolars, incisors, or canines. Despite the ubiquity and perceived simplicity of the method, cementum annuli analysis can be time-consuming, expensive, inaccurate, and imprecise, and require specialized equipment. Using beavers (Castor canadensis) as a test species, we developed a straightforward method to age mammals that requires little specialized equipment. The method consists of: (1) digitizing longitudinally sectioned teeth and measuring the proportion of tooth surface area comprised of cementum (“proportion cementum”), (2) evaluating the relationship between proportion cementum and specimen age (determined from either known-age samples or cementum annuli analysis), and (3) using the modeled relationship to estimate the age of other individuals based solely on proportion cementum. The relationship between proportion cementum and age was strongly correlated (R² = .97–.98 depending on observer), similar between observers, and similar between known-age specimens and those aged via cementum annuli analysis. Using this proportion cementum method, two independent observers accurately predicted the age of 80%–84% of specimens within 0.5 year and 96%–98% within 1 year. We suggest this aging method will likely work with most mammal species given the relatively consistent deposition of cementum throughout mammals' lives and has promise to be a simple and quick alternative to cementum annuli analysis regardless of whether one develops proportion cementum models using known-age specimens or those aged via alternative methods.