Effect of long-term treatment of hyperactive children with methylphenidate.

Summary: Three groups of hyperactive children were compared by various measures of outcome 5 years after initial evaluation: 24 who were treated with methylphenidate for 3 to 5 years during the follow-up period, 22 treated with chlorpromazine for 18 months to 5 years, and 20 who had received no medication during the follow-up period. The three groups were matched with respect to age, IQ, socioeconomic class and sex. No statistically significant differences were found between the three groups on the following measures of outcome: emotional adjustment, delinquency, Wechsler Intelligence Scale for Children, Bender Gestalt visual-motor test and academic performance (as measured by number of grades failed). Initially there was a significant difference between the three groups on ratings of hyperactivity and family diagnosis. Hyperactivity scores decreased significantly over the 5 years; family diagnosis ratings changed little. Analysis of covariance for these two measures showed no difference in degree of improvement between the three groups. Our impression was that methylphenidate was helpful in making hyperactive children more manageable at home and at school, but did not significantly affect their outcome after 5 years of treatment.     

Who is Responsible for Fission in a Free-ranging Troop of Baboons?

The study troop of chacma baboons (Papio cynocephalus ursinus) at Mkuzi Game Reserve, Zululand, South-Africa, comprised of about 76 members that split into two new troops. The events leading to this troop fission will be described and its possible causes will be discussed. Troop fission among baboons is generally attributed to the withdrawal of low-ranking females from the main group, as a result of the cost of food competition and its effect on their reproductive success. At Mkuzi, no evidence for food competition among females was recorded in terms of rank-related time spent feeding or other time—budget components, feeding-bout length, diet composition or context of female aggression. Moreover, no evidence for rank-related differential reproductive success was found in terms of inter-birth intervals or infant survival. Female mortality was, however, related to dominance rank, with circumstantial evidence suggesting that cause of mortality was predation by leopards. Rate of female disappearances, aggression levels among females, and the percentage of time they spent in proximity to other adult troop members increased after fission. Relatively short inter-birth intervals and extremely low infant mortality rate at Mkuzi resulted in a small number of receptive females at any one time, and therefore in high costs of male sexual competition as expressed in the high levels of male aggression and woundings, both reduced after fission. It is suggested that this troop fission may have been initiated by the resident males, triggered by the high cost of sexual competition, and forced on the females, who were, consequently, subjected to higher risk of predation. The troop fission was preceded by a long process of increasing tendency for sub-trooping. It was initiated by the four resident males who kept a large distance apart from each other, herded oestrous female associates away from others and were followed by other females. The females generally tended to stay close to associates, males and females. These parties were followed by the peripheral and immigrant males who had no female associates, and eventually two distinct daughter troops were formed.     

Incorporating physiology into species distribution models moderates the projected impact of warming on selected Mediterranean marine species

Species distribution models (SDMs) correlate species occurrences with environmental predictors, and can be used to forecast distributions under future climates. SDMs have been criticized for not explicitly including the physiological processes underlying the species response to the environment. Recently, new methods have been suggested to combine SDMs with physiological estimates of performance (physiology-SDMs). In this study, we compare SDM and physiology-SDM predictions for select marine species in the Mediterranean Sea, a region subjected to exceptionally rapid climate change. We focused on six species and created physiology-SDMs that incorporate physiological thermal performance curves from experimental data with species occurrence records. We then contrasted projections of SDMs and physiology-SDMs under future climate (year 2100) for the entire Mediterranean Sea, and particularly the ‘warm’ trailing edge in the Levant region. Across the Mediterranean, we found cross-validation model performance to be similar for regular SDMs and physiology-SDMs. However, we also show that for around half the species the physiology-SDMs substantially outperform regular SDM in the warm Levant. Moreover, for all species the uncertainty associated with the coefficients estimated from the physiology-SDMs were much lower than in the regular SDMs. Under future climate, we find that both SDMs and physiology-SDMs showed similar patterns, with species predicted to shift their distribution north-west in accordance with warming sea temperatures. However, for the physiology-SDMs predicted distributional changes are more moderate than those predicted by regular SDMs. We conclude, that while physiology-SDM predictions generally agree with the regular SDMs, incorporation of the physiological data led to less extreme range shift forecasts. The results suggest that climate-induced range shifts may be less drastic than previously predicted, and thus most species are unlikely to completely disappear with warming climate. Taken together, the findings emphasize that physiological experimental data can provide valuable supplemental information to predict range shifts of marine species.     

Variation in phosphorus and sulfur content shapes the genetic architecture and phenotypic associations within the wheat grain ionome

Dissection of the genetic basis of wheat ionome is crucial for understanding the physiological and biochemical processes underlying mineral accumulation in seeds, as well as for efficient crop breeding. Most of the elements essential for plants are metals stored in seeds as chelate complexes with phytic acid or sulfur‐containing compounds. We assume that the involvement of phosphorus and sulfur in metal chelation is the reason for strong phenotypic correlations within ionome. Adjustment of element concentrations for the effect of variation in phosphorus and sulfur seed content resulted in drastic change of phenotypic correlations between the elements. The genetic architecture of wheat grain ionome was characterized by quantitative trait loci (QTL) analysis using a cross between durum and wild emmer wheat. QTL analysis of the adjusted traits and two‐trait analysis of the initial traits paired with either P or S considerably improved QTL detection power and accuracy, resulting in the identification of 105 QTLs and 617 QTL effects for 11 elements. Candidate gene search revealed some potential functional associations between QTLs and corresponding genes within their intervals. Thus, we have shown that accounting for variation in P and S is crucial for understanding of the physiological and genetic regulation of mineral composition of wheat grain ionome and can be implemented for other plants.     

COPII collar defines the boundary between ER and ER exit site and does not coat cargo containers

COPII and COPI mediate the formation of membrane vesicles translocating in opposite directions within the secretory pathway. Live-cell and electron microscopy revealed a novel mode of function for COPII during cargo export from the ER. COPII is recruited to membranes defining the boundary between the ER and ER exit sites, facilitating selective cargo concentration. Using direct observation of living cells, we monitored cargo selection processes, accumulation, and fission of COPII-free ERES membranes. CRISPR/Cas12a tagging, the RUSH system, and pharmaceutical and genetic perturbations of ER-Golgi transport demonstrated that the COPII coat remains bound to the ER–ERES boundary during protein export. Manipulation of the cargo-binding domain in COPII Sec24B prohibits cargo accumulation in ERES. These findings suggest a role for COPII in selecting and concentrating exported cargo rather than coating Golgi-bound carriers. These findings transform our understanding of coat proteins’ role in ER-to-Golgi transport.     

B lymphocyte inhibition of anti-tumor response depends on expansion of Treg but is independent of B-cell IL-10 secretion

The mechanisms by which B lymphocytes inhibit anti-tumor immunity remain poorly understood. Murine EMT-6 mammary tumors grow readily in immune competent mice (BALB/c), but poorly in B-cell-deficient μ^?/? BALB/c mice (BCDM). T regulatory cell (Treg) expansion and function were impaired in BCDM compared with BALB/c. In this study, we compared tumor growth, Treg cell proliferation, tumor lymphocyte infiltration and cytolytic T cell activity in BALB/c, BCDM and BCDM partially reconstituted with B cells by adoptive transfer (BCDM+B). Partial reconstitution of BCDM with adoptively transferred B cells restored EMT-6 tumor growth, which was independent of IL-10 secretion by B cells. Instead, high frequencies of intratumoral B cells were associated with increased recruitment and proliferation of Treg cells within the tumor microenvironment. The B-cell-dependent accumulation of Treg within the tumor microenvironment was associated with reduced tumor infiltration by CD49+ NK and CD8+ T cells and reduced cytotoxic T cell activity against EMT-6 targets. Our studies indicate that tumor-dependent immunosuppression of T-cell-mediated anti-tumor immunity is coordinated within the tumor microenvironment by B-cell-dependent cross talk with Treg cells, which does not require production of IL-10 by B cells.