Evolution of autoantibody responses via somatic hypermutation outside of germinal centers

Somatically mutated high-affinity autoantibodies are a hallmark of some autoimmune diseases, including systemic lupus erythematosus. It has long been presumed that germinal centers (GCs) are critical in autoantibody production, because they are the only sites currently believed to sustain a high rate of somatic hypermutation. Contrary to this idea, we found that splenic autoreactive B cells in autoimmune MRL.Fas(lpr) mice proliferated and underwent active somatic hypermutation at the T zone-red pulp border rather than in GCs. Our results implicate this region as an important site for hypermutation and the loss of B cell self-tolerance.     

Frequency ratio of Al+ and Hg+ single-ion optical clocks; metrology at the 17th decimal place

Time has always had a special status in physics because of its fundamental role in specifying the regularities of nature and because of the extraordinary precision with which it can be measured. This precision enables tests of fundamental physics and cosmology, as well as practical applications such as satellite navigation. Recently, a regime of operation for atomic clocks based on optical transitions has become possible, promising even higher performance. We report the frequency ratio of two optical atomic clocks with a fractional uncertainty of 5.2 x 10(-17). The ratio of aluminum and mercury single-ion optical clock frequencies nuAl+/nuHg+ is 1.052871833148990438(55), where the uncertainty comprises a statistical measurement uncertainty of 4.3 x 10(-17), and systematic uncertainties of 1.9 x 10(-17) and 2.3 x 10(-17) in the mercury and aluminum frequency standards, respectively. Repeated measurements during the past year yield a preliminary constraint on the temporal variation of the fine-structure constant alpha of alpha/alpha = (-1.6+/-2.3) x 10(-17)/year.     

Feline house soiling: Elimination and marking behaviors

Although challenging at times, managing cats with elimination issues can be rewarding. The frustration in management of these cases is often a result of the lack of a proper diagnosis and random treatment application. A systematic approach to these cases should help to achieve treatment success. Also, new information should lead to further advancements in treatment.     

Studies on the captive breeding of the Knysna seahorse, Hippocampus capensis

Seahorse populations throughout the world are vulnerable toexploitation for use in traditional Chinese medicines. Variouscaptive breeding ventures have been established in attempts tomeet the demand and to reduce the pressure on the naturalpopulations. Many of these programmes have relied on the captureof wild pregnant males which then give birth under captiveconditions. This would however limit production during the non-breeding season. In this study Knysna seahorses, Hippocampuscapensis, were bred in captivity during the non-breeding season(winter) using photothermal manipulation. Three constantphotoperiods (20L:4D, 16L:8D & 12L:12D) were tested incombination with three temperatures (22 °C, 25 °C& 28 °C). All combinations tested were successful inextending the breeding season of H. capensis. The frequency ofpregnancies as well as the number of young produced/pregnancy wasnot affected by the different photoperiod/temperaturecombinations. Each male gave birth to 39.38 ± 20.81juveniles every 34.03 ± 17.25 days during a four monthperiod. The mean juvenile weight and length was influenced by thephotoperiod and/or temperature regimes. Juvenile length decreasedwith increasing temperature (p 0.0001), while an increasein the light phase of the photoperiod regime at 20L:4D resultedin a significant increase (p 0.0006) in length whencompared to the 16L:8D and 12L:12D photoperiods. Juvenile weightdecreased with increasing temperature, while the combination ofphotoperiod 16L:8D and the lowest water temperature (22 °C)yielded the highest mean weights. Further studies are necessaryto determine whether mean juvenile weight or length influencesjuvenile survival     

Effect of the use of dilute alkaline prior to Bacillus subtilis-based biocontrol steeping and germination conditions on red sorghum malt β-glucanase activities and residual β-glucans

Malting is the ideal stage to deal with β-glucans. Their hydrolysis is very important as the diffusion of both hormones and hydrolytic enzymes in the endosperm of germinated grain depend on it. A high malt β-glucanase activity is not a guarantee of an extensive hydrolysis of β-glucans. When Bacillus subtilis is used to control mould growth, red sorghum malt β-glucanase activity (measured using carboxymethylcellulose as the substrate) was improved without significantly affecting the hydrolysis of malt β-glucans. Thus, in order to reduce the residual β-glucans content, soaking in 0.2% NaOH was combined with a biocontrol. Soaking in 0.2% NaOH is recognized as capable of improving grain hydration by opening-up the endosperm cell walls. The combined use of 0.2% NaOH with B. subtilis-based biocontrol treatments during red sorghum malting, leads to malt with increased β-glucanase activity and a significant reduction of residual β-glucans when compared with the 16 h biocontrol steeping without prior steeping in 0.2% NaOH. β-glucanase activity increases with increased germination temperature and time while, conversely, the residual β-glucans content of the malts decreases. Indeed, while the level of β-glucanase was not vastly different between the malts obtained after steeping in distilled water and those obtained after 8 h steeping in 0.2% NaOH followed by 8 h resteeping in distilled water (NaOH + H₂O treatment), their residual β-glucans levels differ significantly. B. subtilis-based treatment leads to malt with improved β-(1-3)- and β-(1-4)-glucanase activities without significantly improved malt β-(1-3),(1-4)-glucanase activity. While malts obtained after 84 h germination weren't significantly different in terms of malt β-(1-3),(1-4)-glucanase activities for all steeping treatments, the use of 0.2% NaOH steeping prior to resteeping led to malts with improved β-glucans content. Combining the steeping in dilute alkaline and biocontrol enables taking advantage of the dilute alkaline effect on residual β-glucans content, due probably to the opening-up of the cell walls and the improvement of water uptake, and that of the biocontrol (improvement of β-glucanase synthesis).     

Surgical management of orbital nodular granulomatous episcleritis in a dog

A 27 kg, 6‐year‐old, male castrated German shorthaired pointer presented to the University of Missouri, Veterinary Teaching Hospital with the complaint of progressive exophthalmia of 2 years duration optical density (OD). Lack of retropulsion OD was noted on physical examination. Anterior segment examination OU and fundic examination OS did not reveal any abnormalities. Examination of the fundus OD revealed focal scleral indentation of the inferior nasal globe. The indentation changed location with globe movement OD. MRI and CT scan revealed a well‐circumscribed, approximately 2 cm in diameter mass located caudal and ventral to the affected globe that appeared to communicate with the nictitating membrane with absence of any bony involvement. A modified lateral orbitotomy was recommended and performed to remove the orbital mass and nictitating membrane en‐bloc. Histopathology and immunohistochemistry of the mass confirmed a diagnosis of nodular granulomatous episcleritis (NGE). Postoperatively, the dog developed absolute keratoconjunctivitis sicca (KCS). Examples of primary episcleral inflammation in the dog include diffuse episcleritis, NGE, nodular fasciitis, fibrous histiocytoma, proliferative conjunctivitis/keratoconjunctivitis, pseudotumor, and Collie granuloma. The etiology of these episcleral inflammations is presumed to be immune mediated. To our knowledge, this is the first report of NGE affecting the orbital region of a dog. Development of absolute KCS resulting from excision of the nictitating membrane is also supported by this case.     

The sedative effects of low-dose medetomidine and butorphanol alone and in combination intravenously in dogs

ObjectiveTo evaluate the sedative effects of intravenous (IV) medetomidine (1 μg kg^?1) and butorphanol (0.1 mg kg^?1) alone and in combination in dogs.Study designProspective, blinded, randomized clinical trial.AnimalsSixty healthy (American Society of Anesthesiologists I) dogs, aged 6.2 ± 3.2 years and body mass 26 ± 12.5 kg.MethodsDogs were assigned to four groups: Group S (sodium chloride 0.9% IV), Group B (butorphanol IV), Group M (medetomidine IV) and Group MB (medetomidine and butorphanol IV). The same clinician assessed sedation before and 12 minutes after administration using a numerical scoring system in which 19 represented maximum sedation. Heart rate (HR), respiratory rate, pulse quality, capillary refill time and rectal temperature were recorded after each sedation score assessment. Sedation scores, sedation score difference (score after minus score before administration) and patient variables were compared using one-way anova for normally distributed variables and Kruskal–Wallis test for variables with skewed distributions and/or unequal variances. Where significance was found, further evaluation used Bonferroni multiple comparisons for pair-wise testing.ResultsBreed, sex, neuter status, age and body mass did not differ between groups. Sedation scores before substance administration were similar between groups (p = 0.2). Sedation scores after sedation were significantly higher in Group MB (mean 9.5 ± SD 5.5) than in group S (2.5 ± 1.8) (p < 0.001), group M (3.1 ± 2.5) (p < 0.001) and group B (3.7 ± 2.0) (p = 0.003). Sedation score difference was significantly higher in Group MB [7 (0–13)] than in Group S [0 (?1 to 4)] (p < 0.001) and Group M [0 (0–6)] (p < 0.001). HR decreased significantly in Groups M and MB compared with Group S (p < 0.05).Conclusion and clinical relevanceLow-dose medetomidine 1 μg kg^?1 IV combined with butorphanol 0.1 mg kg^?1 IV produced more sedation than medetomidine or butorphanol alone. HR was significantly decreased in both medetomidine groups.