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Figure 4. Maternal attendance affects South American fur seal pup’s growth rate, energy balance, and immune response against hookworms. ; (A) The observed number of nursing events against predicted values of growth rate. With more nursing events pups grow faster (GLM.NB, 0.031 ± 0.006, Z = 5.53, p = 3.2×10−8). (B) Pups that survived hookworm infection had higher levels of maternal attendance (more nursing events) (GLM.NB, 0.78 ± 0.23, Z = 3.45, p = 5.5×10−4), faster growth rate (GLM.NB, 1.05 ± 0.16, Z = 6.6, p = 2.7×10−11), and higher average levels of glucose (GLM, 3.0 ± 0.5, Z = 5.9, p = 1.02×10−7) compared to pups that died from hookworm disease; however, they had similar attendance and metabolic values compared to hookworm-free (control) pups (GLM.NB, 0.01 ± 0.13, Z = 0.13, p = 0.893, and GLM, 0.71 ± 0.38, t = 1.863, p = 0.066). (C) The observed values of number of nursing events, growth rate, interaction between nursing and growth rate and hookworm burden vs. the predicted values of CD3+ lymphocytes in section of skin in response to phytohemagglutinin (PHA) challenge. Pups with more nursing events (GLM.NB, 0.098 ± 0.02, Z = 4.39, p = 1.14×10−5), faster growth rate (GLM.NB, 0.04 ± 0.004, Z = 11.3, p = 2.0×10−16), and higher hookworm burden (GLM.NB, 0.009 ± 0.004, Z = 2.56, p = 0.01) had more recruitment of T-lymphocytes. (D) A subset of pups was divided into groups of low and high response to PHA challenge at 30 days old. Pups with higher CD3 lymphocyte response had higher average levels of parasite-specific IgG (GLM.NB, 1.11 ± 0.33, Z = 3.37, p = 7.5×10−4), shorter infectious period (GLM.NB, −0.38 ± 0.12, Z = −3.06, p = 2.1×10−3), faster growth rate (GLM.NB, 0.68 ± 0.06, Z = 10.9, p = 2.0×10−16), and higher levels of maternal attendance (GLM.NB, 0.94 ± 0.13, Z = 7.04, p = 1.92×10−1). Hookworm burden was similar between the two groups (GLM.NB, low reactivity = −0.63 ± 0.37, Z = −1.67, p = 0.09). Raw data: Figure 4—source data 1 and Figure 4—source data 2.

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Figure 1. The mutant mouse had intermittent dystonic behaviors affecting hindlimbs and tail. ; (A) During ambulation, hyperextension could affect either hindlimb or both, sometimes with inversion of the foot. When hyperextension was unilateral, some mice had a preferred side et al. switched sides. Hyperextension of hindlimbs was seen at the youngest age during locomotion, but by 4 months of age was sometimes seen at rest and sometimes was bilateral. A bilateral, maximally extended posture is within a WT mouse’s normal repertoire because it is shown by nursing dams straddling a large litter. (B) Hyperextension often continued when the animals sat. (C) Briefly curved tail was sometimes the first symptom in weanlings but was seen in older adults mainly when stressed. The curvature, in the plane of the floor, utilizes lateral muscle groups, and Straub tail was seldom if ever seen. (D) While WT mice sometimes have brief periods of rigidity and tilting when dropped in water, the mutant mice adopted an upright posture with extreme hyperextension and spread toes. They soon recovered and swam. (E) The normal WT reflex when suspended by the tail. (F) Mutants exhibited caudal hyperextensions involving one or both hindlimbs. This is also within the normal repertoire because WT exhibit a hindlimb posture like this when suspended just out of reach of an object and reaching with the forelimbs. (G) The mutants also exhibited transient hyperflexions of one or both hindlimbs. This was not a coordinated 'clasped' posture (limbs held together at the midline). Vibration stimulation of the knee joint in awake, hand-held mutant mice sometimes elicited strong dystonic movements when mice were released (not shown).

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