SUMMARYWe studied how short-term milk synthesis responds to milk removal by observing breast volume before and after each breastfeed over 24 h periods within the homes of seven lactating mothers, using the Computerized Breast Measurement system. Short-term rates of milk synthesis varied markedly between the breasts of individual mothers, varied markedly between interfeed intervals for individual breasts and, for six of the thirteen breasts studied, were positively related to the degree to which the breast was emptied (r2 ranging from 0-32 to 0 95). In addition, the infants rarely emptied the breasts of available milk (mean + S.D. of degree of emptying postfeed = 76 + 20 %, n = 147) and, within women, storage capacity of a breast was related to the demand for milk from that breast (r2 = 0-91, P < 0-0001). It was concluded that the infants were self-regulating their milk intake. Furthermore, the storage capacity of the breast, variations in the short-term rates of milk synthesis and responsiveness of milk synthesis to the degree of breast emptying provided mechanisms whereby maternal milk supply could be directly linked to infant demand. Our findings are discussed with reference to the autocrine control of milk synthesis.

Radiotherapy is essential to the treatment of most solid tumors and acquired or innate resistance to this therapeutic modality is a major clinical problem. Here we show that miR-139-5p is a potent modulator of radiotherapy response in breast cancer via its regulation of genes involved in multiple DNA repair and reactive oxygen species defense pathways. Treatment of breast cancer cells with a miR-139-5p mimic strongly synergized with radiation both and, resulting in significantly increased oxidative stress, accumulation of unrepaired DNA damage, and induction of apoptosis. Several miR-139-5p target genes were also strongly predictive of outcome in radiotherapy-treated patients across multiple independent breast cancer cohorts. These prognostically relevant miR-139-5p target genes were used as companion biomarkers to identify radioresistant breast cancer xenografts highly amenable to sensitization by cotreatment with a miR-139-5p mimetic. The microRNA described in this study offers a potentially useful predictive biomarker of radiosensitivity in solid tumors and a generally applicable druggable target for tumor radiosensitization. .

Cytomegalovirus infection is a frequent and life-threatening complication that significantly limits positive transplantation outcomes. We developed preclinical mouse models of cytomegalovirus reactivation after transplantation and found that humoral immunity is essential for preventing viral recrudescence. Preexisting antiviral antibodies decreased after transplant in the presence of graft-versus-host disease and were not replaced, owing to poor reconstitution of donor B cells and elimination of recipient plasma cells. Viral reactivation was prevented by the transfer of immune serum, without a need to identify and target specific antigenic determinants. Notably, serotherapy afforded complete protection, provided that the serum was matched to the infecting viral strain. Thus, we define the mechanisms for cytomegalovirus reactivation after transplantation and identify a readily translatable strategy of exceptional potency, which avoids the constraints of cellular therapies.