Body temperature regulation in a desert lizard, Sauromalus obesus, under undisturbed field conditions

1. Mean selected body temperatures (MSBTs), measured by radiotelemetry, are presented for 15 chuckwallas on 26 animal days. 2. MSBT, during the period of activity, ranged from 37.3 to 39.8 degrees C (means = 38.8 +/- 0.2 SE degrees C) while MSBTs, from the time lizards attained their first high set point to the time that solar radiation ceased, ranged from 36.1 to 39.6 degrees C (means = 38.3 +/- 0.2 SE degrees C). 3. On cloudy, cool days, animals could not maintain high Tbs because of the absence of solar radiation. 4. On sunny March and April days, animals were active for 5-6 hr but Tb then fell rapidly to low levels. 5. From late April to mid May, animals were active for 7-8 hr and Tbs did not fall as drastically because of higher Tas after sunset. 6. August was the time of year (for this study) when chuckwallas had the highest effective 24 hr Tb but it was also the time when they had the shortest activity interval.     

Glutamine repeats and inherited neurodegenerative diseases: molecular aspects

Several dominantly inherited, late onset, neurodegenerative diseases are due to expansion of CAG repeats, leading to expansion of glutamine repeats in the affected proteins. These proteins are of very different sizes and, with one exception, show no sequence homology to known proteins or to each other; their functions are unknown. In some, the glutamine repeat starts near the N-terminus, in another near the middle and in another near the C-terminus, but regardless of these differences, no disease has been observed in individuals with fewer than 37 repeats, and absence of disease has never been found in those with more than 41 repeats. Protein constructs with more than 41 repeats are toxic to E. coli and to CHO cells in culture, and they elicit ataxia in transgenic mice. These observations argue in favour of a distinct change of structure associated with elongation beyond 37–41 glutamine repeats. The review describes experiments designed to find out what these structures might be and how they could influence the properties of the proteins of which they form part. Poly- -glutamines form pleated sheets of β-strands held together by hydrogen bonds between their amides. Incorporation of glutamine repeats into a small protein of known structure made it associate irreversibly into oligomers. That association took place during the folding of the protein molecules and led to their becoming firmly interlocked by either strand- or domain-swapping. Thermodynamic considerations suggest that elongation of glutamine repeats beyond a certain length may lead to a phase change from random coils to hydrogen-bonded hairpins. Possible mechanisms of expansion of CAG repeats are discussed in the light of looped DNA model structures.     

Fungal--bacterial interactions: a mixed bag of mingling microbes

Fungi and bacteria co-inhabit a wide variety of environments, from soils and food products to plants and mammals. Interactions between bacteria and fungi can have dramatic effects on the survival, colonization and pathogenesis of these organisms. There are instances where bacteria provide fungi with compounds that enhance the production of fungal virulence determinants. Other bacteria produce factors that are likely to inhibit pathogenesis by repressing fungal filamentation. Furthermore, mixed bacterial-fungal biofilms can have properties that are distinct from their single-species counterparts. Clinical studies, in combination with in vitro model systems, are necessary to understand how bacterial-fungal interactions impact human health.     

Lentiviral gene transfer into the dorsal root ganglion of adult rats

Background

Neuronal hyperexcitability is a crucial phenomenon underlying spontaneous and evoked pain. In invertebrate nociceptors, the S-type leak K⁺ channel (analogous to TREK-1 in mammals) plays a critical role of in determining neuronal excitability following nerve injury. Few data are available on the role of leak K_2P channels after peripheral axotomy in mammals.

Results

Here we describe that rat sciatic nerve axotomy induces hyperexcitability of L4-L5 DRG sensory neurons and decreases TRESK (K2P18.1) expression, a channel with a major contribution to total leak current in DRGs. While the expression of other channels from the same family did not significantly change, injury markers ATF3 and Cacna2d1 were highly upregulated. Similarly, acute sensory neuron dissociation (in vitro axotomy) produced marked hyperexcitability and similar total background currents compared with neurons injured in vivo. In addition, the sanshool derivative IBA, which blocked TRESK currents in transfected HEK293 cells and DRGs, increased intracellular calcium in 49% of DRG neurons in culture. Most IBA-responding neurons (71%) also responded to the TRPV1 agonist capsaicin, indicating that they were nociceptors. Additional evidence of a biological role of TRESK channels was provided by behavioral evidence of pain (flinching and licking), in vivo electrophysiological evidence of C-nociceptor activation following IBA injection in the rat hindpaw, and increased sensitivity to painful pressure after TRESK knockdown in vivo.

Conclusions

In summary, our results clearly support an important role of TRESK channels in determining neuronal excitability in specific DRG neurons subpopulations, and show that axonal injury down-regulates TRESK channels, therefore contributing to neuronal hyperexcitability.     

Genetics in the study of mosquito susceptibility to Plasmodium

Within the past several years, a number of powerful genetic and genomic tools have been developed for use in research on the African malaria vector Anopheles gambiae. While these tools have been developed with a broad range of potential applications in mind, they have been particularly useful in advancing the effort to clone a set of An. gambiae genes that enable a refractory strain of this mosquito to encapsulate and kill a wide variety of different malaria parasites to which this mosquito is normally fully susceptible. This paper describes the latest progress in this map-based cloning research, which involves the collaborative contributions of a number of different laboratories in Europe and the United States.     

Spatially restricted patterns of expression of the homeobox-containing gene Hox 2.1. during mouse embryogenesis

The mouse Hox 2.1 gene contains a homeobox sequence and is therefore a candidate for a vertebrate gene involved in the control of embryonic patterning or positional specification. To investigate this possibility, we have used in situ hybridization to determine the pattern of Hox 2.1 expression during mouse embryogenesis. At 8.5 days post coitum, Hox 2.1 is expressed at a low level in the posterior neuroectoderm and mesoderm, and in the neuroectoderm of the presumptive hindbrain. At 12.5 days p.c., Hox 2.1 is expressed in an anteroposterior restricted domain extending from the hindbrain throughout the length of the spinal cord, predominantly in the dorsal region. Between 12.5 and 13.5 days p.c. the domain becomes localized to the occipital and cervical regions. We also detect Hox 2.1 RNA in the embryonic lung, stomach, mesonephros and metanephros, as well as in myenteric plexus, dorsal root ganglia and the nodose ganglion, and in mature granulocytes. The embryonic expression of Hox 2.1 in neural tissue is compared with that of Hox 3.1, which also shows anteroposterior restricted domains of gene expression. These patterns of expression are not clearly consistent with Hox 2.1 or Hox 3.1 having roles in segmental patterning. However, the data are consistent with these genes having regulatory roles in anteroposterior positional specification in the neuroectoderm and mesoderm, and suggest that Hox 2.1 may also have functions during organogenesis.     

Clinical Features of Reported Ethylene Glycol Exposures in the United States

Background

Ethylene glycol is highly toxic and represents an important cause of poisonings worldwide. Toxicity can result in central nervous system dysfunction, cardiovascular compromise, elevated anion gap metabolic acidosis and acute kidney injury. Many states have passed laws requiring addition of the bittering agent, denatonium benzoate, to ethylene glycol solutions to reduce severity of exposures. The objectives of this study were to identify differences between unintentional and intentional exposures and to evaluate the utility of denatonium benzoate as a deterrent.

Methods and Findings

Using the National Poison Data System, we performed a retrospective analysis of reported cases of ethylene glycol exposures from January 2006 to December 2013. Outcome classification was summed for intentionality and used as a basis for comparison of effect groups. There were 45,097 cases of ethylene glycol exposures resulting in 154 deaths. Individuals more likely to experience major effects or death were older, male, and presented with more severe symptoms requiring higher levels of care. Latitude and season did not correlate with increased exposures; however, there were more exposures in rural areas. Denatonium benzoate use appeared to have no effect on exposure severity or number.

Conclusion

Deaths due to ethylene glycol exposure were uncommon; however, there were major clinical effects and more exposures in rural areas. Addition of denatonium benzoate was not associated with a reduction in exposures. Alternative means to deter ingestion are needed. These findings suggest the need to consider replacing ethylene glycol with alternative and less toxic agents.     

Src kinases relax adherens junctions between the neighbors of apoptotic cells to permit apical extrusion

Epithelia can eliminate apoptotic cells by apical extrusion. This is a complex morphogenetic event where expulsion of the apoptotic cell is accompanied by rearrangement of its immediate neighbors to form a rosette. A key mechanism for extrusion is constriction of an actomyosin network that neighbor cells form at their interface with the apoptotic cell. Here we report a complementary process of cytoskeletal relaxation that occurs when cortical contractility is down-regulated at the junctions between those neighbor cells themselves. This reflects a mechanosensitive Src family kinase (SFK) signaling pathway that is activated in neighbor cells when the apoptotic cell relaxes shortly after injury. Inhibiting SFK signaling blocks both the expulsion of apoptotic cells and the rosette formation among their neighbor cells. This reveals the complex pattern of spatially distinct contraction and relaxation that must be established in the neighboring epithelium for apoptotic cells to be extruded.