Equitable maritime boundary delimitation,as exemplified in the work of the international court of justice during the presidency of sir Robert Yewdall Jennings and Beyond

The article contains a systematic survey of decisions rendered by the International Court of Justice (and its Chamber) under the presidency of Sir Robert Yewdall Jennings in three cases (Guinea Bissau v. Senegal, Gulf of Fonseca, and Denmark v. Norway,) involving equitable maritime delimitation, and in one case (East Timor) settled after Sir Robert's presidency. Distinct features, which are particularly pronounced in the landmark Denmark v. Norway Judgment, are the increased consistency and degree of predictability in the complex process of applying equity in maritime delimitation, of which Sir Robert has been a strong advocate. The important procedural aspects of the case law under Sir Robert's presidency are also analyzed. These are exemplified by the role of the Court as a partner in preventive diplomacy and by the precedential permission granted a third state to intervene as a nonparty. While highlighting the two presently pending cases (Qatar/Bahrain and Cameroon v. Nigeria), the author hopes that these settlements will significantly benefit from substantial and procedural solutions endorsed by the Court during Sir Robert's presidency.     

The zoogeographical composition and distribution of the Arabian termite fauna

Thirty-three termite species have been recorded from the Arabian peninsula (from Saudi Arabia, North and South Yemen, Oman, Bahrain, Abu Dhabi, Qatar and Kuwait). The fauna is predominantly Afro-tropical (Ethiopian) but with a major Palaearctic (Eremic) element. The greatest diversity occurs in the south-west where mountainous regions provide greater habitat diversity than elsewhere. The Afro-tropical influence decreases towards the north and east, the Palaearctic influence increasing correspondingly; the Oriental influence is negligible and the level of endemism is high.     

Mental health services in the Arab world

This paper summarizes the current situation of mental health services in the Arab world. Out of 20 countries for which information is available, six do not have a mental health legislation and two do not have a mental health policy. Three countries (Lebanon, Kuwait and Bahrain) had in 2007 more than 30 psychiatric beds per 100,000 population, while two (Sudan and Somalia) had less than 5 per 100,000. The highest number of psychiatrists is found in Qatar, Bahrain and Kuwait, while seven countries (Iraq, Libya, Morocco, Somalia, Sudan, Syria and Yemen) have less than 0.5 psychiatrists for 100,000 population. The budget allowed for mental health as a percentage from the total health budget, in the few countries where information is available, is far below the range to promote mental health services. Some improvement has occurred in the last decade, but the mental health human resources and the attention devoted to mental health issues are still insufficient.     

The Mauritian Piracy Act: A Comment on the Director of Public Prosecutions v Ali Abeoulkader Mohamed Decision

In 2011 Mauritius adopted the Piracy and Maritime Violence Act (the Act). The Act does not expressly state that Mauritian Courts have jurisdiction over offenses committed outside of Mauritius. In Director of Public Prosecutions v Ali Abeoulkader Mohamed & Ors, the Mauritian Supreme Court dealt with the issue of whether the Act applied to non-Mauritius citizens where the alleged piracy acts had been committed outside of Mauritius on the high seas. This article assesses the Supreme Court's decision and suggest ways that the Act can be strengthened.     

A Note on the M/V “Louisa” Case

In the M/V “Louisa” case of 28 May 2013, the International Tribunal for the Law of the Sea held that it had no jurisdiction, even though it had established prima facie jurisdiction at the provisional measures stage. The M/V “Louisa” case thus gives rise to questions regarding the relationship between prima facie jurisdiction and jurisdiction on the merits. Moreover, the M/V “Louisa” Judgment also sheds some light on the applicability of the doctrine of abuse of rights provided in Article 300 of the UN Convention on the Law of the Sea.     

A Tribunal Navigating Complex Waters: Implications of the Bay of Bengal Case

The International Tribunal on the Law of the Sea's March 2012 Judgment in the Bay of Bengal Case is a landmark decision in multiple ways. It represents the first maritime boundary to be delimitated by the Tribunal. It is the first adjudication of a maritime boundary in Asia, and it is also the first judicial delimitation of a maritime boundary for parts of the extended continental shelf located seaward of the 200-nautical-mile limit from baselines. While the Tribunal's ruling largely resolves the maritime dispute between Bangladesh and Myanmar, it also raises a number of questions and concerns that are highlighted in this article, including the Tribunal's approach to delimitation both within and beyond the 200-nautical-mile limit, the treatment of islands, the interplay between law of the sea institutions and the creation of a so-called grey area where continental shelf jurisdiction falls to one state and water column jurisdiction to the other.     

Between global citizenship and Qatarization: negotiating Qatar's new knowledge economy within American branch campuses

Over the last decade, the Gulf state of Qatar has invested billions of dollars in American branch campuses as part of its development as a ‘knowledge-based economy’. A knowledge economy will allow Qatar to diversify from petroleum wealth and reduce the country's reliance on foreign labour by introducing more citizens into the workforce, a process called ‘Qatarization’. While intended to bolster nativism, branch campuses are organized around certain Western liberal norms, such as meritocracy, egalitarianism and multiculturalism. These manifest in several ways, including English education, gender integration and a student body that is composed of more non-citizens than Qatari nationals. In this article, I explore how non-citizen students in particular, many of who were born and raised in Qatar, interact with Qatar's new knowledge economy, paying particular attention to the seemingly contradictory models of ‘global citizenship’ on the one hand and ‘Qatarization’ on the other – one a philosophy that is open and inclusive, and the other specifically closed and exclusive.     

KSR Int'l Co. v. Teleflex, Inc.: no obvious changes for the biotechnology market

With the advent of molecular biology, genomics, and proteomics, the intersection between science and law has become increasingly significant. In addition to the ethical and legal concerns surrounding the collection, storage, and use of genomic data, patent disputes for new biotechnologies are quickly becoming part of mainstream business discussions. Under current patent law, new technologies cannot be patented if they are “obvious” changes to an existing patent. The definition of “obvious,” therefore, has a huge impact on determining whether a patent is granted. For example, are modifications to microarray protocols, popular in diagnostic medicine, considered “obvious” improvements of previous products? Also, inventions that are readily apparent now may not have been obvious when discovered. Polymerase chain reaction, or PCR, is now a common component of every biologist’s toolbox and seems like an obvious invention, though it clearly was not in 1983. Thus, there is also a temporal component that complicates the interpretation of an invention’s obviousness. The following article discusses how a recent Supreme Court decision has altered the definition of “obviousness” in patent disputes. By examining how the obviousness standard has changed, the article illuminates how legal definitions that seem wholly unrelated to biology or medicine could still potentially have enormous effects on these fieldsJust what is obvious or not is a question that has provoked substantial litigation in the Federal Circuit, the appellate court with special jurisdiction over patent law disputes. Under U.S. patent law, an inventor may not obtain a patent, which protects his invention from infringement by others, if the differences between the subject matter sought to be patented and the prior art are such that “the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill” in the patent’s subject matter area [1]. However, what was “obvious” at the time of invention to a person of ordinary skill is hardly clear and is, in effect, a legal fiction designed to approximate objectivity. As illustrated by Chief Justice John Roberts of the Supreme Court in a moment of levity, “Who do you get to ... tell you something’s not obvious … the least insightful person you can find?” [2] Despite the apparent objectivity provided by a “person of ordinary skill” obviousness standard, the difficulty lies in that such a standard is still susceptible to multiple interpretations, depending on the point of view and knowledge ascribed to the “ordinary person.” As such, how obviousness is defined and interpreted by the courts will have important implications on biotechnology patents and the biotechnology business.The issue of obviousness arose in April 2007 when the Supreme Court handed down its decision in KSR Int’l Co. v. Teleflex, Inc. [3] The facts of the case were anything but glamorous; in the suit, Teleflex, a manufacturer of adjustable pedal systems for automobiles, sued KSR, its rival, for infringement of its patent, which “describe[d] a mechanism for combining an electronic sensor with an adjustable automobile pedal so that the pedal’s position can be transmitted to a computer that controls the throttle in the vehicle’s engine.” [4] Teleflex believed that KSR’s new pedal design was too similar to its own patented design and therefore infringed upon it [5]. In defense, KSR argued that Teleflex’s patent was merely the obvious combination of two pre-existing elements and, thus, the patent, upon which Teleflex’s infringement claim was based, was invalid.Patent law relies on the concept of obviousness to distinguish whether new inventions are worthy of being protected by a patent. If a new invention is too obvious, it is not granted a patent and is therefore not a legally protected property interest. However, if an invention is deemed not obvious and has met the other patentability requirements, a patent will be granted, thereby conferring exclusive use of the invention to the patent holder. This exclusive right prohibits others from making, using, selling, offering to sell, or importing into the United States the patented invention [6]. Essentially, the definition of obviousness sets the balance between rewarding new inventions with exclusive property rights and respecting old inventions by not treating minor variations of existing patents as new patents. In this manner, the law seeks to provide economic incentives for the creation of new inventions by ensuring that the property right conferred by the patent will be protected against insignificant variations. The importance of where the line for obviousness is drawn and how clearly it is drawn is especially important in the biotechnology industry. Studies have shown that the development of a new pharmaceutical therapy can take up to 14 years with costs exceeding $800 million [7]. Such an enormous investment of time and money would not be practical if it did not predictably result in a legally enforceable property right.The standard for what constitutes a patentable discovery has evolved over the last 150 years. In 1851, the Supreme Court held in Hotchkiss v. Greenwood that a patentable discovery required a level of ingenuity above that possessed by an ordinary person [8]. Lower courts treated the Hotchkiss standard as a subjective standard, whereby courts sought to determine “what constitute[d] an invention” [9] and a “flash of creative genius” [10]. However, the attempts at imposing the Hotchkiss standard proved unworkable, and in 1952, Congress overrode the case law with the Patent Act, “mandat[ing] that patentability be governed by an objective nonobviousness standard.” [11] This new statutory standard moved the courts away from subjective determinations and toward a more workable, objective obviousness standard.While the Patent Act laid the foundation for the current obviousness standard, the Supreme Court in Graham v. John Deere Co. interpreted the statutory language in an attempt to provide greater clarity as to what exactly “obvious” meant [12]. The Supreme Court determined that the objective analysis would require “the scope and content of the prior art ... to be determined; differences between the prior art and the claims at issue ... to be ascertained; and the level of ordinary skill in the pertinent art resolved.” [13] In addition to analysis under this three-part framework, the Supreme Court called for several secondary considerations to be weighed, including “commercial success, long felt but unresolved needs, [and the] failure of others [to solve the problem addressed].” [13]Unsurprisingly, lower courts were unsatisfied with the Supreme Court’s attempts to clarify the obviousness standard and sought to provide “more uniformity and consistency” to their evaluation of obviousness than the Supreme Court’s jumble of factors provided [14]. In search of consistency, the Federal Circuit created the “teaching, suggestion, or motivation” test (TSM test) “under which a patent is only proved obvious if ‘some motivation or suggestion to combine prior art teachings’ can be found in the prior art, the nature of the problem, or the knowledge of a person having ordinary skill in the art.” [14] Through implementation of the TSM test, the Federal Circuit sought to maintain the flexibility envisioned by the Supreme Court in Graham, while at the same time providing more certainty and predictability to obviousness determinations.The issue before the Supreme Court in KSR Int’l Co. v. Teleflex, Inc. was whether the Federal Circuit’s elaboration on the statutory language of the Patent Act, the TSM test, was consistent with the terms of the Patent Act itself and the Supreme Court’s own analysis in Graham. The Supreme Court determined that while the TSM test was, on its terms, consistent with the framework set out in Graham, the rigid manner in which the Federal Circuit had taken to applying that standard was inconsistent with the flexible approach established by Graham [15]. More generally, it appears the Supreme Court was mainly interested in restoring a more rounded, thorough inquiry to the evaluation of obviousness: “Graham set forth a broad inquiry and invited courts, where appropriate, to look at any secondary considerations that would prove instructive.” [16] As stated by the Supreme Court, “[r]igid preventative rules that deny factfinders recourse to common sense, however, are neither necessary under our case law nor consistent with it.” [17] As such, the Supreme Court reversed the findings of the Federal Circuit, which had found the Teleflex patent valid, and remanded the case back to the lower court with directions to analyze, without rigid adherence to the TSM test, whether the Teleflex patent was obvious [18].The Supreme Court’s ruling in KSR Int’l Co. v. Teleflex, Inc. that the Federal Circuit apply its TSM test less rigidly may have implications for those seeking biotechnology patents in the future. As discussed above, the large investments necessary to develop a marketable biotechnology product demand that entrepreneurs making those investments be reasonably assured that they can predict any future legal hurdles in patenting their invention and in ultimately protecting their patent. As explained by the Biotechnology Industry Organization in its amicus curiae brief in KSR Int’l Co. v. Teleflex, Inc., “[i]nvestment thus is predicated on an expected return on investment in the form of products or services that are protected by patents whose validity can be fairly determined.” [19] Therefore, the Supreme Court’s insistence that the Federal Circuit no longer rigidly rely on the TSM test could increase uncertainty in the grant of future patents. However, the Supreme Court’s refusal to completely dismiss the TSM test, while in fact endorsing its continued use, albeit on a less rigid basis, has to be viewed as a profound victory for an industry with a significant stake in maintaining the status quo. Moreover, it is unclear how much the Supreme Court’s holding in KSR Int’l Co. v. Teleflex, Inc. will truly change the legal analysis of the lower courts, given the evidence that lower courts already were independently shifting away from rigid adherence to the TSM test before the Supreme Court’s ruling [20].More importantly, several aspects of the Supreme Court’s reasoning in KSR Int’l Co. v. Teleflex, Inc. seem to directly address relevant concerns of the biotechnology market in favorable ways. First, the Supreme Court made clear that though a product is the result of a combination of elements that were “obvious to try,” it is not necessarily “obvious” under the Patent Act. Retaining the possibility that “obvious to try” inventions still may be patentable is extremely important to the biotechnology industry in particular because “many patentable inventions in biotechnology spring from known components and methodologies found in [the] prior art.” [21] Rather than foreclosing all “obvious to try” inventions as being obvious, and therefore not patentable, the Supreme Court instead explained that where there is “a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions,” it is more likely that a person of ordinary skill would find it obvious to pursue “known options.” [22] Thus, the proper inquiry, as stated by the Supreme Court, is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” [23] While this reasoning may prevent some “obvious to try” inventions from being patented, it is unlikely to have a substantial effect on inventions in the biotechnology market because “most advances in biotechnology are only won through great effort and expense, and with only a low probability of success in achieving the claimed invention at the outset.” [24] In other words, it would be hard to characterize the use of prior art in the biotechnology context as predictable based on the inherent unpredictability of obtaining favorable results. As such, most biotechnology inventions would presumably fall outside the Supreme Court’s “obvious to try” reasoning due to the very nature of the industry, meaning they would remain patentable under the Supreme Court’s KSR Int’l Co. v. Teleflex, Inc. decision.Second, the Supreme Court recognized the “distortion caused by hindsight bias” and the importance of avoiding “arguments reliant upon ex post reasoning,” though it lessened the Federal Circuit’s rigid protection against hindsight bias [24]. Hindsight bias requires that obviousness be viewed at the time the invention was made, because what may seem revolutionary at the time of invention may, upon the passage of time, seem “obvious.” Cognizance of hindsight bias is crucial for biotechnology patents because “there often is a long ‘passage of time between patent application filing and litigation with biotechnology inventions [that] can exacerbate the problem’ of hindsight bias.” [25] The problem is further exacerbated by the “significantly longer durations of commercial utility” biotechnology inventions enjoy as compared to those in other fields [25]. The more time between the filing of a patent and the subsequent litigation over its validity, the greater the risk that “reliable accounts of [the] context” in which the discovery is made will no longer exist [26]. As such, inventions that were not obvious when they were created will be inescapably colored by the passage of time and by new knowledge and discoveries; the likelihood of this occurrence is higher the further removed the litigation is from the patent filing date. Once again, however, it seems clear that despite the Supreme Court’s abandonment of the TSM test’s rigidity, strong protections against hindsight bias still were emphasized in the Supreme Court’s KSR Int’l Co. v. Teleflex, Inc. decision. In fact, lower courts applying KSR Int’l Co. v. Teleflex, Inc. acknowledge they are “cautious” to avoid “using hindsight” in biotechnology obviousness determinations [27].Finally, the Supreme Court seems to believe that the imposition of a more flexible approach will be more likely to benefit markets not directly at issue in KSR Int’l Co. v. Teleflex, Inc. The Supreme Court asserted, “[t]he diversity of inventive pursuits and of modern technology counsels against limiting the analysis” to the rigid TSM test of the Federal Circuit [28]. This language suggests that the Supreme Court expects lower courts to take into consideration the special considerations facing unique markets, such as the biotechnology market. As such, the specific concerns of the biotechnology market discussed above may receive more attention under the flexible framework asserted by the Supreme Court in KSR Int’l Co. v. Teleflex, Inc.Leading up to the oral argument in KSR Int’l Co. v. Teleflex, Inc., there was widespread speculation that the case could result in a watershed moment, significantly altering the definition of obviousness in patent law. For many, including those in the biotechnology industry, there was ample reason to be concerned. Any change in the definition of obviousness would effectively shift property rights from new patent holders to old, or vice versa. However, the Supreme Court acted with restraint. While the decision purports to make substantial changes by doing away with the Federal Circuit’s TSM test, the opinion seems more like a mild-mannered rebuke of lower courts that had become too complacent in the implementation of their beloved test. If anything, the Supreme Court’s insistence on a more flexible formula is simply a call for lower courts to employ common sense, in addition to considering the factors from Graham and the TSM test. Accordingly, the Supreme Court’s opinion in KSR Int’l Co. v. Teleflex, Inc. is unlikely to have a pronounced effect on the biotechnology market, despite the widespread concern generated before the actual decision was handed down.     

Ernst Mayr: Biologist-historian

Ernst Mayr's historical writings began in 1935 with his essay Bernard Altum and the territory theory and have continued up through his monumentalGrowth of Biological Thought (1982) and hisOne Long Argument: Charles Darwin and the Genesis of Modern Evolutionary Thought (1991). Sweeping in their scope, forceful in their interpretation, enlisted on behalf of the clarification of modern concepts and of a broad view of biology, these writings provide both insights and challenges for the historian of biology. Mayr's general intellectual formation was guided by the GermanBildung ideal, with its emphasis on synthetic and comprehensive knowledge. His understanding of how to write history was inspired further by the example of the historian of ideas Arthur Lovejoy. Some strengths and limitations of this approach are explored here through attention to Mayr's treatment of the French biologist J.-B. Lamarck. It is contended that Mayr's contributions to the history of biology are not restricted to his own very substantial historical writings but also include his encouragement of other scholars, his development of an invaluable archive of scientific correspondence, and his insistence that historians who write about evolution and related subjects acquire an adequate understanding of the principles of Darwinian biology.This paper was originally delivered at the biennial meeting of the International Society for the History, Philosophy, and Social Studies of Biology, held in Brandeis in July 1993, in the special session organized by John Greene on Ernst Mayr's contributions to systematics, evolutionary theory, and the history and philosophy of biology. The paper is presented here with only slight modifications of the original, oral presentation. As indicated in the text, a full assessment of Mayr's historical work, including situating that work in the context of Mayr's other work and contemporary developments in the history of science, would require a much more extensive study than I have been able to undertake here.     

Constitutional values and HIV/AIDS in the workplace: reflections on Hoffman v. South African Airways

South Africa is experiencing an HIV/AIDS epidemic of enormous proportions. The workplace, like all the other sectors, is adversely affected. The tendency of a significant proportion of employers has been to discriminate against employees and job applicants living with HIV/AIDS through use of HIV testing to exclude those that are HIV-positive. In the case of Hoffmann v South African Airways, the Constitutional Court was asked to determine the constitutionality of excluding a job applicant on account of an HIV-positive status. The Court ruled in favour of the applicant and ordered instatement. Through an analysis of Hoffmann v South African Airways, the article examines how constitutional values are impacting on HIV/AIDS-related ethics in the workplace.     

Judgment algorithm for periodicity of time series data based on Bayesian information criterion

Judgment periodicity of biological time series data is important and done widely to find the circadian expression of genes, monthly change of hormones, etc. To keep complete reproducibility of judgment is a problem because popular judgment methods such as curve fitting, Fourier analysis, etc. need judgment criteria determined by analysts considering experimental conditions and results (level, S/N, distribution, etc.) based on their experience. Judgment results are often affected by analysts' subjects. Reproducible criterion determination is therefore strongly needed. We propose introducing the information criterion to replace analysts' criteria. A judgment algorithm by combining Bayesian information criterion (BIC) and discrete Fourier transform (DFT) has been developed and has proved its ability through application to mice microarray data and finding of circadian genes. Our method, named "Piccolo", shows higher sensitivity than the simple DFT (without BIC) method with reproducibility, and can be fully automated.     

Redox-linked proton translocation by direct-coupled ligand conduction

The term direct-coupled is considered in the context of redox-linked proton translocation mechanisms, and the origins of this concept, its philosophical implications, applications, and contributions to the development of bioenergetics, are discussed.     

‘Threatened Fishes of The World’ Series, an Update

The series of one-page articles on the Threatened fishes of the world was launched in 1995 (Bruton 1995, Moyle & Moyle 1995). Since then ichthyologists and fish biologists throughout the world have contributed 97 articles (Environmental Biology of Fishes vol. 43–57, Table 1). In 15 volumes of the journal 37 families have been so far included. The largest number of contributions was on species in the family Cyprinidae (23) followed by Galaxiidae (8). Eighty-four contributions have been on freshwater, seven on estuarine and six on marine fish species (Table 2).     

A model equations of the volume transport of multicomponent and heterogeneous non-ionic solutions in double-membrane system

The volume flows model equation for a double-membrane system, in which two membranes separate three compartments (l,m,r) containing the heterogeneous, non-ionic n-component solutions is elaborated. In this system the solution concentrations fulfill the condition Clk > Cmk > Crk. The inter-membrane compartment (m) consists of the infinitesimal layer of solution. The volume of compartment m and external compartments (l and r) fulfill the conditions Vm 0 and Vl =Vr respectively. The linear dependences of the volume flux on concentration differences in binary solutions and nonlinear – in ternary solutions, were obtained. This model for binary and ternary non-electrolyte solutions is discussed. It is shown, that the double-membrane system has rectifying and amplifying properties for osmotic transport and mechanical pressure.     

Isabela Crater-Lake: a Mexican insular saline lake

Opinion This is a series of contributions, expressing explicit opinions with regard to contemporary topics in limnology. These Opinions are mostly based on new books with a large impact, but can also refer to other currently debated topics. Documented reactions to these contributions should be sent to the editor-in-chief; they will be considered for publication in subsequent issues.     

从Myriad案谈基因专利的正当性及美国对基因专利授权实质性要件分析

按照专利制度构建的本质,基因专利的作用在于激励产业创新,促进基因研究的发展。但基因专利从产生以来就一直存在着争议。2011年美国Myriad案对分离DNA序列的可专利性具有不同的观点,从Myriad I案认为分离的DNA是不可专利的客体,到Myriad II上诉案中联邦巡回上诉法院推翻地方法院的观点,认为分离的DNA具有不同的化学结构,满足专利客体的适格性,但同时也反射出了对DNA序列可专利性的怀疑。Myriad案引起了美国、欧洲和澳大利亚司法审判中就基因专利适格性问题的较大争议。本文结合美国Myriad案来分析DNA序列作为专利客体的适格性以及目前美国对基因专利授权的实质性条件。     

On valuing patches: estimating contributions to metapopulation growth with reverse-time capture-recapture modelling

Metapopulation ecology has historically been rich in theory, yet analytical approaches for inferring demographic relationships among local populations have been few. We show how reverse-time multi-state capture-recapture models can be used to estimate the importance of local recruitment and interpopulation dispersal to metapopulation growth. We use 'contribution metrics' to infer demographic connectedness among eight local populations of banner-tailed kangaroo rats, to assess their demographic closure, and to investigate sources of variation in these contributions. Using a 7 year dataset, we show that: (i) local populations are relatively independent demographically, and contributions to local population growth via dispersal within the system decline with distance; (ii) growth contributions via local survival and recruitment are greater for adults than juveniles, while contributions involving dispersal are greater for juveniles; (iii) central populations rely more on local recruitment and survival than peripheral populations; (iv) contributions involving dispersal are not clearly related to overall metapopulation density; and (v) estimated contributions from outside the system are unexpectedly large. Our analytical framework can classify metapopulations on a continuum between demographic independence and panmixia, detect hidden population growth contributions, and make inference about other population linkage forms, including rescue effects and source-sink structures. Finally, we discuss differences between demographic and genetic population linkage patterns for our system.     

Endocytosis in Drosophila: progress, possibilities, prognostications.

By many outside the field, endocytosis is often perceived as a "house-keeping" function performed via identical mechanisms in yeast and man. Recent discoveries have done much to reduce this misperception. (1) Endocytosis occurs via different mechanisms and different pathways in different cellular contexts. (2) Molecular mechanisms that regulate homologous pathways in unicellular and multicellular organisms show considerable variance. (3) Temporally controlled endocytosis of specific regulatory molecules underlies several important and intricate biological processes including synapse formation, synaptic plasticity, cell fate determination, and morphogen gradient formation. Interactions between endocytosis and cytoskeletal and signaling pathways have been particularly revealing. In this intellectual context, Drosophila has become invaluable as a metazoan genetic model in which to understand the many faces of endocytosis. This review discusses two aspects of work in Drosophila: (a) its contributions toward understanding fundamental mechanisms that underlie the operation of endocytic pathways; (b) how analyses in Drosophila provide insights into varied biological processes regulated by endocytosis. In addition, while offering our commentary on merits and limitations of Drosophila work, we speculate on likely areas for contributions and future research on endocytosis in Drosophila.     

The functional binding epitope of a high affinity variant of human growth hormone mapped by shotgun alanine-scanning mutagenesis: insights into the mechanisms responsible for improved affinity

A high-affinity variant of human growth hormone (hGH(v)) contains 15 mutations within site 1 and binds to the hGH receptor (hGHR) approximately 400-fold tighter than does wild-type (wt) hGH (hGH(wt)). We used shotgun scanning combinatorial mutagenesis to dissect the energetic contributions of individual residues within the hGH(v) binding epitope and placed them in context with previously determined structural information. In all, the effects of alanine substitutions were determined for 35 hGH(v) residues that are directly contained in or closely border the binding interface. We found that the distribution of binding energy in the functional epitope of hGH(v) differs significantly from that of hGH(wt). The residues that contributed the majority of the binding energy in the wt interaction (the so-called binding "hot spot") remain important, but their contributions are attenuated in the hGH(v) interaction, and additional binding energy is acquired from residues on the periphery of the original hotspot. Many interactions that inhibited the binding of hGH(wt) are replaced by interactions that make positive contributions to the binding of hGH(v). These changes produce an expanded and diffused hot spot in which improved affinity results from numerous small contributions distributed broadly over the interface. The mutagenesis results are consistent with previous structural studies, which revealed widespread structural differences between the wt and variant hormone-receptor interfaces. Thus, it appears that the improved binding affinity of hGH(v) site 1 was not achieved through minor adjustments to the wt interface, but rather, results from a wholesale reconfiguration of many of the original binding elements.     

Size-fractionated primary production in the open Southern Ocean in austral spring

Size-fractionated primary production was measured by carbon-14 uptake incubations on three transects between 47°S and 59°30S along 6°W in October/November 1992. Open Antarctic Circumpolar Current and ice-covered Weddell Gyre water showed comparable low productivity (0.3 gCm^–2 day^–1) and size distribution. Picoplankton (<2 m) was the dominant size fraction, contributing approximately half to the total water column production. The significance of larger (>20 m) phytoplankton was only minor. Productivity in the Polar Front Zone north of 50°S, with higher water column stability, was up to 10 times higher with microplankton (>20 m) being predominant. No ice-edge bloom occurred over the 2 months study period; this is explained by non-favourable hydrographic conditions for blooming and the lack of melt-water lenses upon ice retreat. Picoplankton tended to make higher contributions at lower water column stability, and microplankton to make higher contributions at higher stability. Mixing, together with light climate, are discussed as the driving forces for Antarctic primary production and for its size structure.