Induction of a heparin-stimulated serine proteinase in sex accessory gland tumors of the Lobund-Wistar rat.

Induction of new proteinase activities that may process growth factors, modify cell surface receptors, cleave extracellular matrix proteins, etc. is considered fundamental in carcinogenesis. The purpose of this study was to characterize a novel proteinase activity induced in sex accessory gland cancers (about 70% in seminal vesicles) of adult male Lobund-Wistar rats by a single injection of N-nitroso-N-methylurea (NMU; 25mg/kg) followed by implanted testosterone propionate (45mg in silastic tubing every 2months) treatment for 10-14months. A 28kDa proteinase activity was detected in tumor extracts using SDS-gelatin gel zymography with incubations done without CaCl2. Its activity was stimulated 15 fold by heparin (optimal activity 1.5-3.0µg/lane) added to the tissue extract-SDS sample buffer prior to electrophoresis. No 28kDa heparin-stimulated proteinase (H-SP) was found in the dorsal, lateral and anterior (coagulating gland) prostate lobes or seminal vesicles of untreated adult rats, but there was a 26-30kDa Ca(2+)-independent proteinase activity in the ventral prostate that showed limited heparin stimulation. The 28kDa H-SP was completely inhibited by 1.0mM 4-(2-aminoethyl)benzenesulfonylfluoride (AESBF) indicating that it was a serine-type proteinase. Other types of proteinase inhibitors were without effect, including serine proteinase inhibitors benzamidine, tranexamic acid and ε-aminocaproic acid. Proteinase activities of about 28kDa were found with casein, fibrinogen or carboxymethylated transferrin as substrate, however, these activities were not stimulated by heparin. Similar levels of activities of the 28kDa H-SP were found in primary tumors and their metastases, but little/no activity was detected in serum, even from rats with large tumor volume and metastases. These data demonstrate overexpression of a heparin-stimulated 28kDa serine proteinase in the primary tumors of sex accessory gland cancers and their metastases. This proteinase either does not leak into or is inactivated in the blood. The role of this proteinase remains to be determined, but its possible interaction with extracellular glycosaminoglycans could focus its proteolytic activity in the tumor microenvironment and affect tumor growth.

Providing social assistance and humanitarian relief: The case for embracing uncertainty.

Motivation: Social assistance, humanitarian relief, and disaster response increasingly overlap, especially where recurrent crises and persistent conflicts prevail. In such situations, distinctions between risk and uncertainty become especially important. It is critical for policy and practice to shift from focusing on risk assessment and management to embracing uncertainty. Purpose: The article assesses the appropriateness of two approaches to social assistance and humanitarian relief where crises recur and conflicts persist: risk assessment and management; and embracing uncertainty and ignorance. Methods and approach: The article reviews different approaches to social assistance, humanitarian relief, and disaster response, and asks how they are framed. It draws on experiences from programmes offering social assistance, humanitarian relief, and disaster response, highlighting the professional, bureaucratic, and institutional features that influence programme design and functioning. These are compared with "high-reliability" approaches deployed in other critical infrastructure-such as water and energy supply. Findings: Mainstream approaches focus on risk assessment and management, assuming predictability and stability. This is problematic, especially in settings of crisis and conflict where there may be no functioning delivery system for social assistance and relief. The article highlights alternatives to the mainstream risk-focused approaches, which emphasize learning, collaboration, adaptation, and flexibility. Such approaches must build on embedded practices of moral economy, collective action, and mutual care and be supported through professional and institutional capacities that generate reliability. Policy implications: The article suggests a new agenda for the intersection of social assistance, humanitarian relief, and disaster response, which makes uncertainty the focus for rethinking responses at scale, especially in settings affected by crisis and conflict.

Newly evolving pastoral and post-pastoral rangelands of Eastern Africa.

Over the past two decades, the rangelands of Eastern Africa have experienced sweeping changes associated with growing human populations, shifting land use, expanding livestock marketing and trade, and greater investment by domestic and global capital. These trends have coincided with several large shocks that were turning points for how rangeland inhabitants make a living. As livelihoods in the region's rangelands transform in seemingly paradoxical directions, away from customary pastoralist production systems, greater insight is required of how these transformations might affect poverty and vulnerability. This article reviews the state of what is known regarding directions of livelihood change in the rangelands of Eastern Africa, drawing on case studies of structural change in five settings in the region. It considers the implications of long-term change, as well as the emergence of very different livelihood mixes in pastoral rangelands, for efforts to reduce poverty and vulnerability in these places.

Adaptation as a political process: adjusting to drought and conflict in Kenya's drylands.

In this article, we argue that people's adjustments to multiple shocks and changes, such as conflict and drought, are intrinsically political processes that have uneven outcomes. Strengthening local adaptive capacity is a critical component of adapting to climate change. Based on fieldwork in two areas in Kenya, we investigate how people seek to access livelihood adjustment options and promote particular adaptation interests through forming social relations and political alliances to influence collective decision-making. First, we find that, in the face of drought and conflict, relations are formed among individuals, politicians, customary institutions, and government administration aimed at retaining or strengthening power bases in addition to securing material means of survival. Second, national economic and political structures and processes affect local adaptive capacity in fundamental ways, such as through the unequal allocation of resources across regions, development policy biased against pastoralism, and competition for elected political positions. Third, conflict is part and parcel of the adaptation process, not just an external factor inhibiting local adaptation strategies. Fourth, there are relative winners and losers of adaptation, but whether or not local adjustments to drought and conflict compound existing inequalities depends on power relations at multiple geographic scales that shape how conflicting interests are negotiated locally. Climate change adaptation policies are unlikely to be successful or minimize inequity unless the political dimensions of local adaptation are considered; however, existing power structures and conflicts of interests represent political obstacles to developing such policies.